PEC2: Análisis de datos de RNAseq con DESeq2

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Abstract

El transcriptoma es el conjunto de moléculas de ARN -codificantes y no codificantes- presentes en una célula o grupo de células en un momento determinado. Partiendo de muestras de tejido tiroideo sin infiltrar (NIT), con pequeñas infiltraciones focales (SFI) y con infiltraciones extensivas (ELI), pretendemos comparar sus transcriptomas e identificar aquellos genes que están diferencialmente expresados en cada una de las posibles comparaciones (NIT-SFI, NIT-ELI, SFI-ELI). Con este objetivo en mente, se analizarán datos provenientes de RNAseq, una técnica de secuenciación que, en contraste con los microarrays, permite detectar hasta un 25% más de DEG entre condiciones. El procesado de los datos y la búsqueda de DEG se realizará mediante el software estadístico R (versión 3.6.2) y de paquetes del proyecto BioConductor (versión 3.10). Los datos y el código relacionados con el análisis pueden ser consultados en el siguiente repositorio GitHub.

Objetivos

El objetivo del estudio es aportar nueva información y mejorar el conocimiento del efecto que tiene la presencia -en diferente grado- de infiltraciones en el tejido tiroideo. En esta dirección, se pretende identificar -a partir de los counts obtenidos mediante RNAseq- que genes y que vías metabólicas están diferencialmente expresados en cada una de las posibles comparaciones entre las tres condiciones experimentales (NIT, SFI, ELI).

Materiales & Métodos

Materiales

Software

Aunque se ha propuesto el uso del software Galaxy (Afgan et al. 2016) como alternativa para este análisis, nosotros nos hemos decantado por la combinación de R (versión 3.6.2) y BioConductor (versión 3.10). Además, para facilitar el procesado y hacerlo más cómodo visualmente, hemos utilizado la interfaz R-Studio (RStudio Team 2015). En la Tabla 1 se muestra un listado con los paquetes implementados durante el análisis.

Package	Repository	Description	Version
knitr	CRAN	Provides a general-purpose tool for dynamic report generation in R using Literate Programming techniques.	1.28
kableExtra	CRAN	Build complex HTML or ‘LaTeX’ tables using ‘kable()’ from ‘knitr’ and the piping syntax from ‘magrittr’.	1.1.0
readxl	CRAN	Import excel files into R. Supports ‘.xls’ via the embedded ‘libxls’ C library and ‘.xlsx’ via the embedded ‘RapidXML’ C++ library .	1.3.1
ggplot2	CRAN	A system for ‘declaratively’ creating graphics, based on “The Grammar of Graphics”.	3.3.0
citr	CRAN	Functions and an ‘RStudio’ add-in that search ‘Bib(La)TeX’-files or ‘Zotero’ libraries to insert formatted Markdown citations into the current document.	0.3.2
ggrepel	CRAN	Provides text and label geoms for ‘ggplot2’ that help to avoid overlapping text labels. Labels repel away from each other and away from the data points.	0.8.2
gplots	CRAN	Various R programming tools for plotting data.	3.0.3
viridis	CRAN	Implementation of the ‘viridis’ - the default -, ‘magma’, ‘plasma’, ‘inferno’, and ‘cividis’ color maps for ‘R’.	0.5.1
cowplot	CRAN	Provides various features that help with creating publication-quality figures with ‘ggplot2’.	1.0.0
RColorBrewer	CRAN	Creates nice looking color palettes especially for thematic maps.	1.1.2
magritrr	CRAN	The magrittr is a package with two aims: to decrease development time and to improve readability and maintainability of code.	1.5
factoextra	CRAN	Provides some easy-to-use functions to extract and visualize the output of multivariate data analyses.	1.07
cluster	CRAN	Methods for Cluster analysis.	3.14
Biobase	BioConductor	Functions that are needed by many other packages or which replace R functions.	2.46.0
EnhancedVolcano	BioConductor	Here, we present a highly-configurable function that produces publication-ready volcano plots.	1.4.0
ReactomePA	BioConductor	This package provides functions for pathway analysis based on REACTOME pathway database.	1.30.0
org.Hs.eg.db	BioConductor	Genome wide annotation for Human, primarily based on mapping using Entrez Gene identifiers.	3.1
DESeq2	BioConductor	Estimate variance-mean dependence in count data from high-throughput sequencing assays and test for differential expression using the negative binomial distribution.	1.26
AnnotationDbi	BioConductor	Implements a user-friendly interface for querying SQLite-based annotation data packages.	1.48
clusterProfiler	BioConductor	This package implements methods to analyze and visualize functional profiles (GO and KEGG) of gene and gene clusters.	3.14
enrichplot	BioConductor	The ‘enrichplot’ package implements several visualization methods for interpreting functional enrichment results obtained from ORA or GSEA analysis.	1.61

Tabla 1: lista de paquetes utilizados durante el análisis.

Datos

Los datos utilizados para el análisis provienen del portal GTEx (Carithers et al. 2015), un servidor web que subministra datos asociados a estudios relacionados con la expresión de hasta 54 tejidos diferentes. En contraste con lo que vimos en la PEC 1, no tenemos que descargar los datos desde ningún portal o servidor. De hecho, se nos han subministrado un par de archivos (counts.csv, targets.csv) que incluyen -respectivamente- los counts crudos de cada uno de los genes estudiados e información acerca de cada una de las muestras (metadata).

Vamos a centrarnos un poco más en el contenido. Como ya se ha comentado anteriormente, los datos corresponden a un estudio que pretendía identificar que genes están diferencialmente expresados en la tiroides en función de la presencia y el grado de infilitraciones en este tejido. En consecuencia, nos encontramos frente a un diseño factorial de un factor (Grado de infiltración) con 3 niveles (NIT, SFI, ELI). Como veremos posteriormente, antes del preprocesado dispondremos de una matriz cruda con un total de 292 muestras (236 NIT, 42 SFI y 14 ELI) y 5.620210^{4} genes. Sin embargo, una vez seleccionadas -aleatoriamente- las muestras para el análisis, cada nivel conformará un único grupo experimental compuesto de 10 réplicas biológicas y, por lo tanto, el tamaño muestral del experimento será de 30 muestras.

Métodos

El análisis de datos provenientes de RNAseq se puede realizar siguiendo protocolos muy variables. En esta sección del informe se intenta resumir un workflow que gira entorno al paquete DESeq2 (Love, Huber, and Anders 2014) y que está bastante extendido entre la comunidad científica.

Preparando entorno de trabajo

Para facilitar el análisis, intentaremos almacenar todos los datos de origen, resultados y ficheros intermedios utilizando una estructura ramificada y jerarquizada de directorios comprendida en el interior de nuestro directorio de trabajo (C:/Users/USER/Documents/Màster Bioestadística i Bioinfo/Análisis de datos Ómicos/PECS/ADO_PEC2_Marc_Garcia). Principalmente, este subconjunto estará formado por los cuatro directorios siguientes:

• data: contendrá -entre otros- las matrices con los counts (original, subset y subset normalizado) y los ficheros con la información de las muestras (original y subset).

• results: contendrá los resultados generados durante el análisis.

• figures: aquí guardaremos las figuras generadas durante el análisis.

• other: incluirá otro tipo de contenido como la tabla con la información sobre los paquetes utilizados.

Análisis exploratorio

El primer paso del pipeline de análisis consiste en un breve análisis exploratorio para identificar que estructura tienen los datos y cual es su contenido. En esta dirección, hemos utilizado una batería de funciones clásicas de R. Entre estas destacan las funciones View(), str(), head(), colnames() o dim(). Todas estas funciones pertenecen a los paquetes base y utils (R Core Team 2019).

Preprocesado de los datos

Selección de muestras

Para simplificar el análisis a la vez que garantizamos que los resultados obtenidos sean significativos, queremos que la representación de cada grupo se reduzca y sea idéntica. Además, para que los resultados de cada alumno sean ligeramente diferentes, queremos que la selección de estas muestras se haga de forma aleatoria. Consecuentemente, el objetivo de este apartado consiste en seleccionar -del total de muestras y de forma aleatoria- un subset de 30 compuesto por 10 muestras de cada uno de los grupos. Con este objetivo, utilizaremos la sintaxis de los corchetes y las funciones as.character(), set.seed() y sample() del paquete base (R Core Team 2019).

Cambio de nombre muestras

Adicionalmente, esta sección incluye el cambio de nombre de las muestras y el guardado del contenido en un nuevo archivo .csv. Con este objetivo en mente, utilizaremos la sintaxis de corchetes combinada con las funciones colnames(), rownames(), paste0() y write.csv() del paquete base (R Core Team 2019).

Construcción DESeq dataset

Antes de proseguir con el análisis, si queremos utilizar el paquete DESeq2 (Love, Huber, and Anders 2014) para el análisis, debemos generar un objeto de tipo DESeqDataSet. Como veremos más adelante, estos objetos presentan similitudes con la estructura de los ExpressionSet que vimos en la PEC 1. Con este objetivo en mente utilizaremos la función DESeqDataSetFromMatrix(). Como argumentos especificaremos la matriz de counts cruda (countData), los metadatos (colData) y el diseño factorial (design).

Eliminación de genes

Aunque este paso no es estrictamente necesario, con el objetivo de dinamizar el análisis, una de las primeras etapas consiste en eliminar -de los datos crudos- aquellos genes que no están expresados. Dicho de otro modo, pretendemos descartar aquellos genes que tienen -para todas las muestras- un número de counts igual a 0. Alternativamente, podemos decir que nos queremos quedar únicamente con aquellas filas que tengan como mínimo un count (rowSums >= 1). En esta dirección utilizaremos la sintaxis de los corchetes combinada con las funciones rowSums() del paquete base (R Core Team 2019) y counts() del paquete BiocGenerics (Huber et al. 2015).

Estabilización de la varianza

Algunas de la pruebas gráficas -que utilizaremos a continuación para el control de calidad- funcionan mejor con datos homocedáticos. Es decir, con muestras que -independientemente de su media de counts- tienen varianzas o desviaciones estándar parecidas. Ya que la media del número de counts y su varianza siguen -generalmente- una relación positiva, antes de proseguir con el control de calidad, debemos realizar lo que se conoce como estabilización de la varianza. El objetivo de este proceso es -precisamente- transformar los datos para que las muestras tengan varianzas similares. Es importante mencionar que, a parte de permitir el control de calidad, este proceso normaliza los datos. Principalmente, existen dos transformaciones ámpliamente utilizadas: la transformación vst y la transformación rlog. La primera se utiliza para datasets que tienen más de 30 muestras, mientras que la segunda se aplica para aquellos con n < 30. Además, la primera es más rápida y menos sensible a outliers. En consecuencia, nosotros utilizaremos esta transformación. Para implementarla usaremos la función vst() del paquete DESeq2 (Love, Huber, and Anders 2014).

Control de calidad

Una vez eliminados los genes que no están expresados en ninguna de las muestras y transformados/normalizados los datos, es necesario realizar un control para determinar si estos tienen la calidad suficiente para ser posteriormente analizados y si hay alguna muestra problemática. En esta dirección, existe una gran variedad de pruebas que podemos realizar, siendo la gran mayoría pruebas gráficas. Como veremos a continuación, entre las más típicas se encuentran los boxplots, los PCAplots o los dendrogramas.

Boxplots

Una de las alternativas más clásicas y ámpliamente utilizadas para valorar la calidad de las muestras consiste en construir un boxplot que muestre la distribución del número de pseudocounts para cada una de las muestras. De este modo podemos comparar las distribuciones entre muestras, identificando cuales de ellas presentan distribuciones que se alejan de lo esperado. En este informe, para construir los boxplots, utilizaremos la sintaxis del paquete ggplot2 (Wickham 2016).

PCA plots

Otra opción muy interesante consiste en construir un PCA plot. Este tipo de gráficos se basan en aquellas componentes de los datos que son responsables de la mayor parte de la variabilidad observada entre muestras (PCs o componentes principales). Son una muy buena opción para determinar si las muestras de un mismo grupo se agrupan conjuntamente e independientemente del resto de grupos. También permiten detectar que muestras se alejan demasiado de su grupo (outliers) y, consecuentemente, puede ser que deban ser eliminadas. En contraste con lo comentado para el boxplot, para el PCA plot crearemos nuestra propia función (plotPCA3()). Esta función ha sido rescatada de la PEC 1 y ligeramente modificada para que se adapte a nuestras necesidades. Su código se muestra en el annexo.

Dendrogramas

La tercera y última prueba gráfica que utilizaremos para el control de calidad se basa en el clustering jerárquico y la posterior construcción de un dendrograma. Este tipo de gráficos son especialmente potentes para identificar si existen diferencias entre las muestras de los grupos experimentales y si existe alguna muestra que podamos catalogar como outlier. En realidad, este gráfico aporta información que es complementaria a la del PCA plot. Para la construcción del dendrograma utilizaremos las funciones dist() del paquete stats (R Core Team 2019) y las funciones hcut() y fviz_dend() del paquete factoextra (Kassambara and Mundt 2020).

Selección de genes (DEG)

Con la intención de identificar que genes estan diferencialmente expresados entre cada una de las dietas y el control, podemos utilizar diferentes enfoques. Aunque existen algunas alternativas que pasan por la utilización de los paquetes limma (Ritchie et al. 2015) o edgeR (Robinson, McCarthy, and Smyth 2009), nosotros hemos preferido utilizar la librería DESeq2 (Love, Huber, and Anders 2014). A continuación se describen brevemente todos los psos necesarios para generar el modelo lineal e identificar y visualizar aquellos genes que presentan una expresión diferencial entre comparaciones.

Análisis de Expresión diferencial

Realizar un análisis de expresión diferencial con el paquete DESeq2 (Love, Huber, and Anders 2014) es tremendamente fácil. Simplemente debemos aplicar la función DESeq() sobre un objeto de tipo DESeqDataSet, DESeqDataSetFromMatrix o DESeqDataSetFromHTSeqCount. Consecuentemente, esta función realizará un análisis por defecto que incluirá -secuencialmente- la estimación de los size factors, la estimación de la dispersión y la adaptación de un modelo binomial negativo.

Consultando resultados contrastes

Llegados a este punto, una vez hecho el análisis con DESeq(), podemos utilizar la función results() del paquete DESeq2 (Love, Huber, and Anders 2014) para consultar los resultados de cada uno de los contrastes. En esta dirección, es importante utilizar el argumento contrast y especificar -como un vector string de tres entradas- el factor y los dos niveles que queremos utilizar durante el contraste. Como veremos más adelante, el output resultante de results() contiene información similar y tiene en un formato muy parecido a las topTables que vimos en la PEC1.

Otra opción muy interesante que ofrece el output de la función DESeq() es la capacidad de aplicarle la función summary() del paquete base (R Core Team 2019). Esta opción permite -fijado un p-valor ajustado mediante el argumento alpha- obtener una tabla que contiene información, entre otros, sobre el número y porcentaje de genes que están upregulated o downregulated. Es importante tener en mente

Anotación de genes

Ahora ya tenemos construidas las topTables. Sin embargo, la única identificación que tienen las entradas de estas tablas es un identificador de ENSEMBL (ENSEMBL ID). Con el objetivo de asociar cada uno de estos identificadores con el nombre del gen al que pertenecen, utilizaremos la función mapIds() del paquete AnnotationDbi (Pagès et al. 2019) y el paquete org.Hs.eg.db (Carlson 2019). Adicionalemnte, también incorporaremos el identificador de Entrez Gene. Es importante remarcar que es probable que algunos de los geneids de las topTables no sean encontrados en la base de datos y por lo tanto se les asigne un valor NA. Consecuentemente, estas entradas deberán ser eliminadas mediante -por ejemolo- el uso de la función na.omit() del paquete stats (R Core Team 2019).

Exportando resultados

En este punto, si así nos conviene, podemos guardar el contenido de estas topTables en un archivo .csv mediante el uso de la función write.csv() del paquete utils (R Core Team 2019). El contenido de las tres topTables generadas lo guardaremos en el directorio results/topTables presente en nuestro working directory.

Filtrando DEG

A partir de las topTables generadas mediante la función results() podemos filtrar aquellos genes que consideremos como diferencialmente expresados (DEG). Igual que para la PEC 1, consideraremos que estos son aquellos que tienen un p-valor ajustado menor que 0.1 y un log2FC superior o inferior a 2. Para el filtrado podemos utilizar la función which() del paquete BiocGenerics (Huber et al. 2015) y la sintaxis de corchetes.

Volcano plots

La visualización de las tablas de genes diferencialmente expresados (DEG) se puede realizar fácilmente mediante volcano plots. Estos gráficos relacionan el cambio de expresión entre condiciones (log2 FoldChange) con la evidencia estadística (-log10(P-value)), siendo aquellos genes con valores más extremos en el eje x y con valores superiores en el eje y los que tienen una evidencia más fuerte de estar diferencialmente expresados. Una de las funciones más utilizadas para su construcción es volcanoplot() del paquete limma (Ritchie et al. 2015). Aún siendo una buena solución, nosotros hemos preferido emplear la función EnhancedVolcano() del paquete con el mismo nombre (Blighe, Rana, and Lewis 2019). A diferencia de volcanoplot(), EnhancedVolcano() permite dibujar el FDR y los logFC cutoffs, diferenciando las 4 categorías de genes que nos podemos encontrar mediante una paleta de colores. De este modo, es mucho más fácil identificar que genes presentan evidencia de estar diferencialmente expresados y establecer comparaciones entre los resultados de cada una de las comparaciones.

Análisis de significación

Resulta mucho más interesante y fácilmente interpretable estudiar -en vez de los genes uno por uno- que vías metabólicas están diferencialmente expresadas en cada una de las tres comparaciones. Para obtener esta información debemos realizar lo que se conoce como análisis de significación o gene enrichment analysis.

Obtención de listas de vías metabólicas diferencialmente expresados

Aunque no es la única alternativa, el paquete enrichplot (Yu 2019) dispone de funciones que nos permiten generar, para cada comparación, tablas que muestran las vías que presentan evidencias significativas de estar diferencialmente expresadas. Estas tablas, a las que nos vamos a referir como GOtables o pathwaytables contienen -entre otros- el identificador de Gene Ontology, una corta descripción (Description), la proporción de genes differencialmente expresados (GeneRatio), el p-valor (pvalue), el p-valor ajustado (p.adjust) y el q-valor (qvalue) para cada vía. Si ordenamos las vías por p-valor o p-valor ajustado (orden ascendiente), podremos visualizar aquellas con una mayor evidencia de estar diferencialmente expresadas.

Barplots

Uno de las modos más clásicos para representar el contenido de las GOtables o pathwaytables consiste en utilizar barplots. Utilizando la función barplot() del paquete graphics [RCore@2019] directamente sobre el objeto enrichGO, podemos generar un gràfico que muestre el número especificado de vías que tienen una mayor evidencia de estar diferencialmente expresadas. A parte de mostrarse el número de genes que forman cada una de estas vías (largo de la barra) también podemos visualizar -mediante una escala de color- el pvalor que indica la evidencia de que esa vía esté realmente diferencialmente expresada.

Cnetplots

Otra opción muy interesante para representar el contenido de las pathway tables consiste en construir cnetplots mediante la función cnetplot() del paquete enrichplot (Yu 2019). Estos gráficos tienen una estructura en forma de red que permite, además de visualizar que vías metabólicas presentan una mayor evidencia de estar diferencialmente expresadas, identificar las conexiones entre genes que pertenecen a más de una vía. Adicionalmente, si así se desea, también permite classificar, mediante una escala de color, aquellos genes que están sobrexpresados o infraexpresados.

Resultados

Exploración & Preprocesado

En la sección de métodos se ha explicado como eran los datos originales (counts.csv, targets.csv) y como se ha realizado el subset para obtener únicamente información de 30 muestras aleatorias. A continuación, se muestran dos tablas: una que contiene la matriz cruda con los counts de 100/5.620210^{4} genes para las 30 muestras seleccionadas (Tabla 2) y una con los metadatos de estas muestras (Tabla 3).

	NIT_1	NIT_2	NIT_3	NIT_4	NIT_5	NIT_6	NIT_7	NIT_8	NIT_9	NIT_10	SFI_1	SFI_2	SFI_3	SFI_4	SFI_5	SFI_6	SFI_7	SFI_8	SFI_9	SFI_10	ELI_1	ELI_2	ELI_3	ELI_4	ELI_5	ELI_6	ELI_7	ELI_8	ELI_9	ELI_10
ENSG00000223972.4	0	7	2	2	8	0	4	1	3	3	3	2	6	2	3	2	9	6	9	1	0	0	1	0	4	2	5	3	1	3
ENSG00000227232.4	555	401	890	468	636	1487	840	925	517	600	460	430	640	457	1704	491	302	820	568	713	834	825	1472	1002	1325	423	489	1301	775	979
ENSG00000243485.2	1	4	1	1	5	1	0	0	2	1	0	0	4	1	1	2	4	0	1	2	1	1	1	1	1	0	1	1	2	3
ENSG00000237613.2	2	2	0	0	2	0	0	0	1	0	1	0	3	2	1	0	2	1	1	0	1	0	0	0	0	0	3	0	0	2
ENSG00000268020.2	1	0	1	0	2	0	0	0	1	4	2	0	1	0	0	0	2	0	1	0	0	0	0	0	2	2	2	0	0	5
ENSG00000240361.1	1	0	0	1	3	2	2	0	3	0	0	0	3	2	0	0	0	4	0	0	0	1	1	1	1	1	1	1	0	8
ENSG00000186092.4	1	0	2	1	4	2	2	1	2	0	1	0	1	3	0	1	2	5	1	1	0	1	2	0	2	0	3	0	1	3
ENSG00000238009.2	5	6	5	8	4	26	7	17	8	9	7	9	5	9	5	7	10	12	5	18	6	10	38	15	4	18	7	5	10	4
ENSG00000233750.3	11	16	16	16	123	46	26	19	14	25	12	9	16	14	22	4	74	18	14	2	6	21	24	19	8	6	100	7	2	81
ENSG00000237683.5	326	744	1126	528	1400	2032	522	813	154	1184	279	679	415	565	2536	552	674	973	738	511	445	853	2020	602	853	325	523	1132	580	527
ENSG00000268903.1	1	1	6	1	2	7	2	2	1	3	2	1	0	5	9	2	4	0	1	4	2	6	13	2	7	1	2	4	1	1
ENSG00000239906.1	0	10	10	4	13	19	8	2	0	35	7	8	4	10	84	5	8	20	10	8	2	16	25	32	17	4	3	2	4	5
ENSG00000241860.2	31	58	52	71	138	140	42	40	65	80	41	95	66	47	120	102	116	101	67	70	40	94	196	96	94	41	183	46	69	115
ENSG00000222623.1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000241599.1	0	2	0	0	1	0	1	0	2	1	1	0	1	0	4	1	1	4	1	1	0	0	0	0	0	1	1	0	1	3
ENSG00000228463.4	66	40	29	31	113	258	42	58	8	64	16	26	18	64	53	95	16	66	52	7	66	98	52	39	44	42	21	92	5	42
ENSG00000237094.7	36	24	63	21	50	101	30	41	19	69	37	10	26	27	99	39	22	43	30	63	38	58	70	43	64	14	95	16	11	46
ENSG00000250575.1	1	4	2	1	1	6	0	4	4	1	1	4	1	3	3	2	3	6	7	1	1	6	5	6	6	0	2	2	1	2
ENSG00000233653.3	6	5	3	8	16	9	5	2	10	7	6	5	7	3	6	3	8	9	7	5	2	8	7	4	7	2	13	1	5	16
ENSG00000224813.2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000235249.1	0	3	3	0	2	1	0	1	1	1	2	1	0	2	2	0	3	3	2	1	0	1	3	0	0	0	5	0	1	3
ENSG00000269732.1	0	1	1	0	0	0	0	2	0	0	0	1	0	0	1	0	0	0	1	0	0	1	0	0	4	0	1	0	0	0
ENSG00000256186.1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000236601.1	1	1	1	0	1	1	0	0	0	0	1	1	1	0	2	0	2	1	1	0	0	0	0	1	1	1	0	0	0	1
ENSG00000236743.1	1	1	1	0	9	0	0	2	2	0	3	0	3	0	2	2	4	3	3	0	2	1	0	0	2	0	3	1	0	1
ENSG00000236679.2	0	1	1	0	7	2	1	1	4	0	4	2	5	3	2	3	63	2	1	1	0	0	0	1	1	0	7	1	3	7
ENSG00000231709.1	0	0	3	0	9	2	1	2	1	0	2	2	6	0	5	3	5	6	10	0	1	4	2	11	6	2	2	1	2	1
ENSG00000235146.2	1	2	2	2	3	0	2	2	1	0	1	0	1	1	0	0	0	0	2	1	1	0	1	0	2	0	2	19	0	6
ENSG00000239664.2	3	0	2	1	2	1	1	2	0	0	0	0	0	0	2	0	2	2	1	0	0	0	0	0	0	0	0	9	0	5
ENSG00000230021.3	1	0	2	2	9	7	2	5	1	4	3	2	5	1	5	3	3	9	3	2	7	3	2	6	2	4	13	11	0	5
ENSG00000223659.1	1	1	0	0	1	0	0	0	2	1	1	1	0	1	2	1	0	2	2	0	0	0	0	0	2	0	5	0	0	1
ENSG00000225972.1	85	90	44	40	245	65	21820	82	72	66	99	54	137	18178	112	50	198	49	81	37	33	55	54	4678	50	25	132	23	37	330
ENSG00000225630.1	9976	21118	25431	14239	13191	9374	7184	15349	15277	11952	13275	7455	22629	10859	13990	6257	10602	14976	34546	6973	9934	18090	12782	8450	27107	7614	12211	8718	10398	64325
ENSG00000237973.1	763	2056	439	1787	3819	599	13349	1553	3465	732	598	640	3860	8778	841	1202	3276	4620	2456	347	2421	1134	483	136	2583	821	1117	242	232	6292
ENSG00000229344.1	201	317	158	175	646	181	396	262	332	187	265	132	574	188	375	201	320	319	211	132	108	161	164	85	212	88	651	93	125	694
ENSG00000240409.1	87	125	61	45	119	30	117	97	64	40	54	30	136	102	180	60	67	84	75	26	28	28	23	15	874	17	84	17	36	187
ENSG00000248527.1	40212	64520	22403	42558	59705	15094	38541	42834	35428	49856	34733	19953	78315	49299	26600	25829	35965	60613	36803	7805	32781	37487	34261	24593	54523	22813	32813	15457	24181	67070
ENSG00000198744.5	243	268	210	154	19806	152	360	272	263	214	335	181	809	183	665	231	512	322	270	97	146	120	183	43	291	70	656	76	217	910
ENSG00000268663.1	0	0	1	1	1	1	1	0	2	0	1	1	1	0	0	3	1	0	0	2	0	0	0	1	0	1	0	0	1	0
ENSG00000185097.2	1	0	0	0	1	0	2	1	2	0	1	1	0	2	2	0	1	1	1	0	0	1	1	0	1	0	0	1	0	2
ENSG00000229376.3	17	25	11	9	38	44	32	21	14	23	9	5	29	7	20	16	19	22	18	5	15	18	14	20	16	25	37	5	13	23
ENSG00000224956.5	403	143	366	232	281	435	256	347	164	441	385	247	283	9	737	202	79	434	242	243	217	260	331	284	676	130	218	195	204	323
ENSG00000235373.1	17	24	28	13	33	21	23	15	15	29	27	15	28	13	16	9	19	33	35	8	8	11	31	26	15	8	41	11	24	33
ENSG00000223181.1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	1
ENSG00000240618.1	11	3	26	6	0	2	2	0	7	7	5	1	8	1	16	0	9	9	9	0	2	6	14	3	5	0	9	2	3	5
ENSG00000229905.1	0	0	0	2	2	0	4	0	0	1	1	0	0	1	1	0	3	1	0	1	1	0	1	0	0	0	0	1	0	1
ENSG00000228327.2	72	114	106	146	152	72	83	71	73	156	165	72	110	119	135	78	64	147	153	56	75	160	313	196	118	89	140	43	99	213
ENSG00000237491.4	96	113	101	125	306	209	116	53	66	215	159	60	175	153	241	95	152	161	224	64	240	166	638	342	155	108	110	224	90	283
ENSG00000230092.3	12	13	12	16	28	18	5	5	5	11	10	13	18	21	55	18	5	15	37	15	19	10	92	23	9	18	13	18	13	47
ENSG00000269831.1	0	0	0	0	0	0	1	1	0	0	0	0	1	0	1	3	0	1	1	0	1	1	1	1	0	0	0	0	0	0
ENSG00000240453.1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000177757.1	12	41	18	32	47	34	44	7	31	40	72	22	65	28	21	18	36	53	57	30	28	24	81	41	14	42	25	35	18	70
ENSG00000225880.4	297	223	279	158	198	728	317	295	118	401	342	173	271	256	724	184	110	331	249	228	347	411	1385	912	623	175	350	503	172	175
ENSG00000228794.4	1141	1444	1059	1056	1618	2003	1005	1375	1127	1371	2204	1366	1954	1118	1930	798	838	1251	1133	897	660	1033	1475	1710	1579	651	837	802	1499	2125
ENSG00000230368.2	7	1	1	2	11	8	2	8	3	2	3	1	5	3	14	7	2	3	5	3	5	6	0	58	10	0	3	0	4	9
ENSG00000234711.1	0	4	1	0	3	4	5	2	4	0	1	0	3	3	1	3	2	3	1	5	1	3	2	31	2	0	6	46	0	4
ENSG00000269308.1	0	0	0	0	2	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
ENSG00000272438.1	5	1	3	0	8	17	3	20	9	8	3	1	8	2	7	4	3	4	3	2	1	1	26	7	19	2	6	3	3	2
ENSG00000230699.2	26	7	44	10	74	114	32	70	89	26	24	19	58	35	12	27	33	52	9	18	11	26	93	1393	61	23	42	38	28	31
ENSG00000241180.1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000223764.2	166	116	273	103	290	181	198	153	246	244	46	112	247	189	107	99	84	258	92	340	58	86	369	348	192	117	83	173	176	196
ENSG00000187634.6	348	283	286	182	654	3256	349	580	1210	541	58	239	700	336	152	246	115	782	224	761	165	249	573	908	503	430	160	625	364	885
ENSG00000268179.1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000188976.6	3111	4934	3177	3286	4670	7739	2922	3236	3554	5370	5505	2641	4600	3396	5058	3223	2464	4601	4211	2414	2863	2831	5100	4272	6149	3130	3182	4305	3545	5177
ENSG00000187961.9	896	593	890	942	583	3737	854	1056	841	935	618	542	1355	863	2017	507	573	1059	724	656	1411	1234	2404	2519	1752	968	1092	1490	633	1874
ENSG00000187583.6	53	48	37	56	54	150	58	263	64	35	454	111	77	101	300	29	14	151	72	124	89	119	614	304	273	133	63	368	72	231
ENSG00000187642.5	19	31	14	22	27	109	26	89	10	22	97	45	32	25	90	22	16	64	31	77	18	63	207	95	105	46	24	181	72	113
ENSG00000272512.1	318	85	145	175	82	408	190	659	43	121	151	163	107	65	79	18	191	150	196	246	37	75	207	234	250	38	70	106	127	241
ENSG00000188290.6	854	354	725	367	238	810	631	1692	296	842	766	721	387	274	410	200	129	641	642	736	282	186	417	391	450	254	174	426	616	445
ENSG00000231702.2	1	4	1	4	1	17	1	1	1	1	5	2	7	2	3	1	4	1	1	4	15	3	5	2	1	4	25	0	2	6
ENSG00000224969.1	5	4	7	1	4	75	4	20	1	3	1	10	10	2	2	2	2	2	2	4	12	7	11	6	6	2	29	4	1	14
ENSG00000187608.5	614	584	1037	297	632	1380	396	3197	787	755	5505	484	663	710	443	611	174	1050	691	834	716	413	1231	1650	1622	732	353	1051	1034	710
ENSG00000188157.9	13046	17757	13573	14742	12621	40113	13808	13967	13776	16136	19950	19135	18902	18831	21424	9626	7208	17856	19340	9206	10900	12729	13701	21822	23783	9633	17342	10638	17499	10845
ENSG00000217801.5	179	34	186	100	112	183	123	115	166	188	74	72	70	79	254	114	51	162	92	106	361	154	483	158	422	86	229	298	137	178
ENSG00000273443.1	3	2	4	0	5	12	1	17	5	2	7	1	3	1	11	5	2	9	8	0	0	0	11	8	9	0	8	2	0	5
ENSG00000237330.2	3	4	3	1	12	5	9	10	7	5	4	5	7	3	6	6	10	6	4	1	4	0	2	6	8	0	7	5	2	8
ENSG00000131591.13	1647	872	1779	1242	1507	1195	1151	1473	753	1648	2192	1463	1699	1540	2700	985	690	1726	1394	993	757	928	2165	1676	2486	640	750	1832	1267	1514
ENSG00000223823.1	6	3	1	0	16	9	1	3	3	1	0	3	1	4	8	4	8	4	4	4	16	19	81	48	8	15	9	27	6	34
ENSG00000207730.1	0	0	1	2	2	3	0	1	0	1	0	0	2	1	5	0	1	1	0	1	3	0	1	0	2	1	3	0	0	0
ENSG00000207607.1	0	1	0	2	1	1	5	2	2	1	0	0	1	1	0	0	0	1	0	1	1	0	4	0	0	0	0	1	0	2
ENSG00000198976.1	1	0	2	1	1	4	1	0	2	0	1	1	2	7	1	0	1	4	1	0	2	1	2	1	4	1	0	1	0	0
ENSG00000272141.1	338	218	330	544	461	829	613	281	217	552	194	128	511	411	562	162	108	691	493	156	478	333	501	283	450	55	305	158	78	210
ENSG00000205231.1	10	6	8	8	25	10	12	7	3	20	7	2	8	9	19	8	10	22	10	8	19	12	23	12	26	1	9	20	2	38
ENSG00000162571.9	47	14	31	51	75	45	24	36	30	192	61	33	16	20	63	69	14	42	30	31	48	24	51	38	55	3	19	36	12	70
ENSG00000186891.9	32	11	41	23	37	263	14	124	31	28	114	600	22	29	197	39	23	204	66	138	154	127	1312	528	687	270	9	566	98	377
ENSG00000186827.6	366	329	308	362	295	419	83	201	244	252	448	191	95	175	690	120	71	338	407	239	284	219	2053	1042	876	328	138	382	174	549
ENSG00000078808.12	6325	11415	7244	6681	8001	16069	7918	6605	9729	10872	10761	7149	10552	8896	8649	6452	4655	9425	9384	7007	5031	5497	11858	10105	10908	10329	7330	7251	8946	7627
ENSG00000176022.3	767	1634	959	938	1476	1659	840	513	1468	1347	1430	570	1432	1360	661	761	636	1098	1576	817	499	554	1531	1257	1487	1299	623	1014	1271	1491
ENSG00000184163.3	79	44	46	40	76	94	65	50	62	57	194	81	66	69	55	18	16	52	34	83	42	44	50	37	85	41	34	48	32	73
ENSG00000260179.1	24	25	4	19	77	53	24	19	20	25	56	35	46	19	22	23	127	56	27	10	29	43	28	25	27	17	25	13	8	30
ENSG00000160087.16	2038	3378	1713	2236	2740	8086	2342	2341	2989	3222	3355	2407	3557	2605	3422	1696	1484	4060	2864	1664	2342	2287	4604	3685	3637	2710	2202	3297	2186	3400
ENSG00000230415.1	83	48	102	50	68	113	67	48	82	127	32	49	95	94	63	53	30	117	56	40	143	57	220	144	198	60	186	76	53	74
ENSG00000162572.15	1044	332	1193	581	677	2708	772	689	948	1382	265	469	755	1004	1277	526	254	1160	746	826	1617	785	2589	1535	2849	575	1515	918	720	1053
ENSG00000131584.14	6325	3683	5951	3606	4910	9622	3839	5792	3677	6961	2875	3224	7823	5214	5451	3173	2542	4972	5452	4347	3471	4136	8329	9033	8497	3493	2594	5850	4125	5342
ENSG00000169972.7	412	448	350	409	509	947	331	344	439	675	382	328	639	501	750	351	207	811	633	251	267	307	693	664	575	473	278	503	360	747
ENSG00000127054.14	8580	6876	8249	6986	7672	18996	7345	9752	7067	11663	8356	6811	10109	8198	17346	6006	4096	12994	7372	5965	8423	8452	15686	12536	14403	5409	11132	9282	6396	10527
ENSG00000240731.1	305	222	251	282	359	715	267	349	314	466	269	292	356	359	683	269	234	526	343	180	349	311	562	453	422	174	552	253	187	459
ENSG00000224051.2	1224	1655	1574	1198	1578	3155	1159	954	1692	1879	1391	1145	1912	1683	2324	1074	1152	1634	1337	1230	1101	1107	2464	2313	3042	1785	1227	2174	1566	2596
ENSG00000169962.4	103	131	88	73	80	660	115	192	116	112	82	157	99	107	223	63	36	232	100	84	170	241	1481	710	374	391	122	733	112	441
ENSG00000107404.13	5411	4415	5534	4810	4774	17137	4592	5723	4993	6692	5775	5918	7387	5839	9026	3745	3082	8265	6086	3969	3984	4702	7338	8266	8374	3795	5249	5436	4778	6645

Tabla 2: tabla que muestra los 100 primeros genes de la matriz cruda contenida en el archivo counts_sub.csv.

X	Experiment	SRA_Sample	Sample_Name	Grupo_analisis	body_site	molecular_data_type	sex	Group	ShortName	color
NIT_1	SRX624388	SRS645976	GTEX-ZAK1-0726-SM-5HL8Q	1	Thyroid	RNA Seq (NGS)	female	NIT	ZAK1-_NIT	#238A8DFF
NIT_2	SRX567480	SRS626942	GTEX-111CU-0226-SM-5GZXC	1	Thyroid	Allele-Specific Expression	male	NIT	111CU_NIT	#238A8DFF
NIT_3	SRX641246	SRS650218	GTEX-1313W-0726-SM-5EGK1	1	Thyroid	Allele-Specific Expression	female	NIT	1313W_NIT	#238A8DFF
NIT_4	SRX618348	SRS644565	GTEX-13X6H-0526-SM-5LU4Q	1	Thyroid	RNA Seq (NGS)	female	NIT	13X6H_NIT	#238A8DFF
NIT_5	SRX199266	SRS333318	GTEX-PX3G-2626-SM-2I3EG	1	Thyroid	RNA Seq (NGS)	female	NIT	PX3G-_NIT	#238A8DFF
NIT_6	SRX628518	SRS648208	GTEX-13PDP-1026-SM-5L3FA	1	Thyroid	RNA Seq (NGS)	male	NIT	13PDP_NIT	#238A8DFF
NIT_7	SRX578920	SRS629748	GTEX-11P7K-0226-SM-5986Z	1	Thyroid	RNA Seq (NGS)	male	NIT	11P7K_NIT	#238A8DFF
NIT_8	SRX633577	SRS648785	GTEX-1269C-0226-SM-5EGKS	1	Thyroid	RNA Seq (NGS)	female	NIT	1269C_NIT	#238A8DFF
NIT_9	SRX570501	SRS627527	GTEX-1399R-0126-SM-5IFEV	1	Thyroid	RNA Seq (NGS)	male	NIT	1399R_NIT	#238A8DFF
NIT_10	SRX630361	SRS648411	GTEX-13112-0326-SM-5P9IW	1	Thyroid	Allele-Specific Expression	male	NIT	13112_NIT	#238A8DFF
SFI_1	SRX614680	SRS644012	GTEX-13O1R-0826-SM-5J2MB	2	Thyroid	RNA Seq (NGS)	male	SFI	13O1R_SFI	#DCE319FF
SFI_2	SRX597654	SRS637303	GTEX-139UW-0126-SM-5KM1B	2	Thyroid	Allele-Specific Expression	male	SFI	139UW_SFI	#DCE319FF
SFI_3	SRX558144	SRS623916	GTEX-11EQ9-0626-SM-5A5K1	2	Thyroid	RNA Seq (NGS)	male	SFI	11EQ9_SFI	#DCE319FF
SFI_4	SRX622888	SRS645805	GTEX-S341-0226-SM-5S2VG	2	Thyroid	RNA Seq (NGS)	female	SFI	S341-_SFI	#DCE319FF
SFI_5	SRX221390	SRS389060	GTEX-TSE9-0626-SM-3DB8B	2	Thyroid	RNA Seq (NGS)	female	SFI	TSE9-_SFI	#DCE319FF
SFI_6	SRX567279	SRS626844	GTEX-12ZZY-0826-SM-5EQMT	2	Thyroid	RNA Seq (NGS)	male	SFI	12ZZY_SFI	#DCE319FF
SFI_7	SRX204008	SRS374961	GTEX-R55C-0626-SM-2TF4Q	2	Thyroid	Allele-Specific Expression	male	SFI	R55C-_SFI	#DCE319FF
SFI_8	SRX260552	SRS408366	GTEX-WYVS-0326-SM-3NM9V	2	Thyroid	RNA Seq (NGS)	female	SFI	WYVS-_SFI	#DCE319FF
SFI_9	SRX407488	SRS524425	GTEX-XMK1-0626-SM-4B65A	2	Thyroid	RNA Seq (NGS)	male	SFI	XMK1-_SFI	#DCE319FF
SFI_10	SRX596158	SRS636581	GTEX-ZE7O-1126-SM-57WC8	2	Thyroid	Allele-Specific Expression	female	SFI	ZE7O-_SFI	#DCE319FF
ELI_1	SRX607358	SRS639491	GTEX-14AS3-0226-SM-5Q5B6	3	Thyroid	RNA Seq (NGS)	female	ELI	14AS3_ELI	#481567FF
ELI_2	SRX601511	SRS638114	GTEX-13QJC-0826-SM-5RQKC	3	Thyroid	Allele-Specific Expression	female	ELI	13QJC_ELI	#481567FF
ELI_3	SRX615373	SRS644099	GTEX-YFC4-2626-SM-5P9FQ	3	Thyroid	Allele-Specific Expression	female	ELI	YFC4-_ELI	#481567FF
ELI_4	SRX582762	SRS631169	GTEX-13NZ9-1126-SM-5MR37	3	Thyroid	RNA Seq (NGS)	male	ELI	13NZ9_ELI	#481567FF
ELI_5	SRX583148	SRS631283	GTEX-YJ89-0726-SM-5P9F7	3	Thyroid	RNA Seq (NGS)	male	ELI	YJ89-_ELI	#481567FF
ELI_6	SRX568916	SRS627158	GTEX-14BMU-0226-SM-5S2QA	3	Thyroid	Allele-Specific Expression	female	ELI	14BMU_ELI	#481567FF
ELI_7	SRX199272	SRS333099	GTEX-PLZ4-1226-SM-2I5FE	3	Thyroid	RNA Seq (NGS)	female	ELI	PLZ4-_ELI	#481567FF
ELI_8	SRX628009	SRS648152	GTEX-11NV4-0626-SM-5N9BR	3	Thyroid	RNA Seq (NGS)	male	ELI	11NV4_ELI	#481567FF
ELI_9	SRX575932	SRS629299	GTEX-14ABY-0926-SM-5Q5DY	3	Thyroid	Allele-Specific Expression	male	ELI	14ABY_ELI	#481567FF
ELI_10	SRX222429	SRS389623	GTEX-TMMY-0826-SM-33HB9	3	Thyroid	Allele-Specific Expression	female	ELI	TMMY-_ELI	#481567FF

Tabla 3: tabla que muestra los metadatos relacionados con las 30 muestras seleccionadas.

Filtrando genes no expresados

Una vez creado el objeto DESeqDataSet, se ha realizado un filtrado con el objetivo de eliminar aquellos genes que no están expresados en ninguna de las 30 muestras. Este filtrado ha permitido eliminar 9421 genes, pasando de a 46781. A continuación se muestran los primeros 100 genes de la matriz de counts filtrada (Tabla 4).

	NIT_1	NIT_2	NIT_3	NIT_4	NIT_5	NIT_6	NIT_7	NIT_8	NIT_9	NIT_10	SFI_1	SFI_2	SFI_3	SFI_4	SFI_5	SFI_6	SFI_7	SFI_8	SFI_9	SFI_10	ELI_1	ELI_2	ELI_3	ELI_4	ELI_5	ELI_6	ELI_7	ELI_8	ELI_9	ELI_10
ENSG00000223972.4	0	7	2	2	8	0	4	1	3	3	3	2	6	2	3	2	9	6	9	1	0	0	1	0	4	2	5	3	1	3
ENSG00000227232.4	555	401	890	468	636	1487	840	925	517	600	460	430	640	457	1704	491	302	820	568	713	834	825	1472	1002	1325	423	489	1301	775	979
ENSG00000243485.2	1	4	1	1	5	1	0	0	2	1	0	0	4	1	1	2	4	0	1	2	1	1	1	1	1	0	1	1	2	3
ENSG00000237613.2	2	2	0	0	2	0	0	0	1	0	1	0	3	2	1	0	2	1	1	0	1	0	0	0	0	0	3	0	0	2
ENSG00000268020.2	1	0	1	0	2	0	0	0	1	4	2	0	1	0	0	0	2	0	1	0	0	0	0	0	2	2	2	0	0	5
ENSG00000240361.1	1	0	0	1	3	2	2	0	3	0	0	0	3	2	0	0	0	4	0	0	0	1	1	1	1	1	1	1	0	8
ENSG00000186092.4	1	0	2	1	4	2	2	1	2	0	1	0	1	3	0	1	2	5	1	1	0	1	2	0	2	0	3	0	1	3
ENSG00000238009.2	5	6	5	8	4	26	7	17	8	9	7	9	5	9	5	7	10	12	5	18	6	10	38	15	4	18	7	5	10	4
ENSG00000233750.3	11	16	16	16	123	46	26	19	14	25	12	9	16	14	22	4	74	18	14	2	6	21	24	19	8	6	100	7	2	81
ENSG00000237683.5	326	744	1126	528	1400	2032	522	813	154	1184	279	679	415	565	2536	552	674	973	738	511	445	853	2020	602	853	325	523	1132	580	527
ENSG00000268903.1	1	1	6	1	2	7	2	2	1	3	2	1	0	5	9	2	4	0	1	4	2	6	13	2	7	1	2	4	1	1
ENSG00000239906.1	0	10	10	4	13	19	8	2	0	35	7	8	4	10	84	5	8	20	10	8	2	16	25	32	17	4	3	2	4	5
ENSG00000241860.2	31	58	52	71	138	140	42	40	65	80	41	95	66	47	120	102	116	101	67	70	40	94	196	96	94	41	183	46	69	115
ENSG00000222623.1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000241599.1	0	2	0	0	1	0	1	0	2	1	1	0	1	0	4	1	1	4	1	1	0	0	0	0	0	1	1	0	1	3
ENSG00000228463.4	66	40	29	31	113	258	42	58	8	64	16	26	18	64	53	95	16	66	52	7	66	98	52	39	44	42	21	92	5	42
ENSG00000237094.7	36	24	63	21	50	101	30	41	19	69	37	10	26	27	99	39	22	43	30	63	38	58	70	43	64	14	95	16	11	46
ENSG00000250575.1	1	4	2	1	1	6	0	4	4	1	1	4	1	3	3	2	3	6	7	1	1	6	5	6	6	0	2	2	1	2
ENSG00000233653.3	6	5	3	8	16	9	5	2	10	7	6	5	7	3	6	3	8	9	7	5	2	8	7	4	7	2	13	1	5	16
ENSG00000235249.1	0	3	3	0	2	1	0	1	1	1	2	1	0	2	2	0	3	3	2	1	0	1	3	0	0	0	5	0	1	3
ENSG00000269732.1	0	1	1	0	0	0	0	2	0	0	0	1	0	0	1	0	0	0	1	0	0	1	0	0	4	0	1	0	0	0
ENSG00000256186.1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000236601.1	1	1	1	0	1	1	0	0	0	0	1	1	1	0	2	0	2	1	1	0	0	0	0	1	1	1	0	0	0	1
ENSG00000236743.1	1	1	1	0	9	0	0	2	2	0	3	0	3	0	2	2	4	3	3	0	2	1	0	0	2	0	3	1	0	1
ENSG00000236679.2	0	1	1	0	7	2	1	1	4	0	4	2	5	3	2	3	63	2	1	1	0	0	0	1	1	0	7	1	3	7
ENSG00000231709.1	0	0	3	0	9	2	1	2	1	0	2	2	6	0	5	3	5	6	10	0	1	4	2	11	6	2	2	1	2	1
ENSG00000235146.2	1	2	2	2	3	0	2	2	1	0	1	0	1	1	0	0	0	0	2	1	1	0	1	0	2	0	2	19	0	6
ENSG00000239664.2	3	0	2	1	2	1	1	2	0	0	0	0	0	0	2	0	2	2	1	0	0	0	0	0	0	0	0	9	0	5
ENSG00000230021.3	1	0	2	2	9	7	2	5	1	4	3	2	5	1	5	3	3	9	3	2	7	3	2	6	2	4	13	11	0	5
ENSG00000223659.1	1	1	0	0	1	0	0	0	2	1	1	1	0	1	2	1	0	2	2	0	0	0	0	0	2	0	5	0	0	1
ENSG00000225972.1	85	90	44	40	245	65	21820	82	72	66	99	54	137	18178	112	50	198	49	81	37	33	55	54	4678	50	25	132	23	37	330
ENSG00000225630.1	9976	21118	25431	14239	13191	9374	7184	15349	15277	11952	13275	7455	22629	10859	13990	6257	10602	14976	34546	6973	9934	18090	12782	8450	27107	7614	12211	8718	10398	64325
ENSG00000237973.1	763	2056	439	1787	3819	599	13349	1553	3465	732	598	640	3860	8778	841	1202	3276	4620	2456	347	2421	1134	483	136	2583	821	1117	242	232	6292
ENSG00000229344.1	201	317	158	175	646	181	396	262	332	187	265	132	574	188	375	201	320	319	211	132	108	161	164	85	212	88	651	93	125	694
ENSG00000240409.1	87	125	61	45	119	30	117	97	64	40	54	30	136	102	180	60	67	84	75	26	28	28	23	15	874	17	84	17	36	187
ENSG00000248527.1	40212	64520	22403	42558	59705	15094	38541	42834	35428	49856	34733	19953	78315	49299	26600	25829	35965	60613	36803	7805	32781	37487	34261	24593	54523	22813	32813	15457	24181	67070
ENSG00000198744.5	243	268	210	154	19806	152	360	272	263	214	335	181	809	183	665	231	512	322	270	97	146	120	183	43	291	70	656	76	217	910
ENSG00000268663.1	0	0	1	1	1	1	1	0	2	0	1	1	1	0	0	3	1	0	0	2	0	0	0	1	0	1	0	0	1	0
ENSG00000185097.2	1	0	0	0	1	0	2	1	2	0	1	1	0	2	2	0	1	1	1	0	0	1	1	0	1	0	0	1	0	2
ENSG00000229376.3	17	25	11	9	38	44	32	21	14	23	9	5	29	7	20	16	19	22	18	5	15	18	14	20	16	25	37	5	13	23
ENSG00000224956.5	403	143	366	232	281	435	256	347	164	441	385	247	283	9	737	202	79	434	242	243	217	260	331	284	676	130	218	195	204	323
ENSG00000235373.1	17	24	28	13	33	21	23	15	15	29	27	15	28	13	16	9	19	33	35	8	8	11	31	26	15	8	41	11	24	33
ENSG00000223181.1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	1
ENSG00000240618.1	11	3	26	6	0	2	2	0	7	7	5	1	8	1	16	0	9	9	9	0	2	6	14	3	5	0	9	2	3	5
ENSG00000229905.1	0	0	0	2	2	0	4	0	0	1	1	0	0	1	1	0	3	1	0	1	1	0	1	0	0	0	0	1	0	1
ENSG00000228327.2	72	114	106	146	152	72	83	71	73	156	165	72	110	119	135	78	64	147	153	56	75	160	313	196	118	89	140	43	99	213
ENSG00000237491.4	96	113	101	125	306	209	116	53	66	215	159	60	175	153	241	95	152	161	224	64	240	166	638	342	155	108	110	224	90	283
ENSG00000230092.3	12	13	12	16	28	18	5	5	5	11	10	13	18	21	55	18	5	15	37	15	19	10	92	23	9	18	13	18	13	47
ENSG00000269831.1	0	0	0	0	0	0	1	1	0	0	0	0	1	0	1	3	0	1	1	0	1	1	1	1	0	0	0	0	0	0
ENSG00000177757.1	12	41	18	32	47	34	44	7	31	40	72	22	65	28	21	18	36	53	57	30	28	24	81	41	14	42	25	35	18	70
ENSG00000225880.4	297	223	279	158	198	728	317	295	118	401	342	173	271	256	724	184	110	331	249	228	347	411	1385	912	623	175	350	503	172	175
ENSG00000228794.4	1141	1444	1059	1056	1618	2003	1005	1375	1127	1371	2204	1366	1954	1118	1930	798	838	1251	1133	897	660	1033	1475	1710	1579	651	837	802	1499	2125
ENSG00000230368.2	7	1	1	2	11	8	2	8	3	2	3	1	5	3	14	7	2	3	5	3	5	6	0	58	10	0	3	0	4	9
ENSG00000234711.1	0	4	1	0	3	4	5	2	4	0	1	0	3	3	1	3	2	3	1	5	1	3	2	31	2	0	6	46	0	4
ENSG00000269308.1	0	0	0	0	2	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
ENSG00000272438.1	5	1	3	0	8	17	3	20	9	8	3	1	8	2	7	4	3	4	3	2	1	1	26	7	19	2	6	3	3	2
ENSG00000230699.2	26	7	44	10	74	114	32	70	89	26	24	19	58	35	12	27	33	52	9	18	11	26	93	1393	61	23	42	38	28	31
ENSG00000223764.2	166	116	273	103	290	181	198	153	246	244	46	112	247	189	107	99	84	258	92	340	58	86	369	348	192	117	83	173	176	196
ENSG00000187634.6	348	283	286	182	654	3256	349	580	1210	541	58	239	700	336	152	246	115	782	224	761	165	249	573	908	503	430	160	625	364	885
ENSG00000268179.1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
ENSG00000188976.6	3111	4934	3177	3286	4670	7739	2922	3236	3554	5370	5505	2641	4600	3396	5058	3223	2464	4601	4211	2414	2863	2831	5100	4272	6149	3130	3182	4305	3545	5177
ENSG00000187961.9	896	593	890	942	583	3737	854	1056	841	935	618	542	1355	863	2017	507	573	1059	724	656	1411	1234	2404	2519	1752	968	1092	1490	633	1874
ENSG00000187583.6	53	48	37	56	54	150	58	263	64	35	454	111	77	101	300	29	14	151	72	124	89	119	614	304	273	133	63	368	72	231
ENSG00000187642.5	19	31	14	22	27	109	26	89	10	22	97	45	32	25	90	22	16	64	31	77	18	63	207	95	105	46	24	181	72	113
ENSG00000272512.1	318	85	145	175	82	408	190	659	43	121	151	163	107	65	79	18	191	150	196	246	37	75	207	234	250	38	70	106	127	241
ENSG00000188290.6	854	354	725	367	238	810	631	1692	296	842	766	721	387	274	410	200	129	641	642	736	282	186	417	391	450	254	174	426	616	445
ENSG00000231702.2	1	4	1	4	1	17	1	1	1	1	5	2	7	2	3	1	4	1	1	4	15	3	5	2	1	4	25	0	2	6
ENSG00000224969.1	5	4	7	1	4	75	4	20	1	3	1	10	10	2	2	2	2	2	2	4	12	7	11	6	6	2	29	4	1	14
ENSG00000187608.5	614	584	1037	297	632	1380	396	3197	787	755	5505	484	663	710	443	611	174	1050	691	834	716	413	1231	1650	1622	732	353	1051	1034	710
ENSG00000188157.9	13046	17757	13573	14742	12621	40113	13808	13967	13776	16136	19950	19135	18902	18831	21424	9626	7208	17856	19340	9206	10900	12729	13701	21822	23783	9633	17342	10638	17499	10845
ENSG00000217801.5	179	34	186	100	112	183	123	115	166	188	74	72	70	79	254	114	51	162	92	106	361	154	483	158	422	86	229	298	137	178
ENSG00000273443.1	3	2	4	0	5	12	1	17	5	2	7	1	3	1	11	5	2	9	8	0	0	0	11	8	9	0	8	2	0	5
ENSG00000237330.2	3	4	3	1	12	5	9	10	7	5	4	5	7	3	6	6	10	6	4	1	4	0	2	6	8	0	7	5	2	8
ENSG00000131591.13	1647	872	1779	1242	1507	1195	1151	1473	753	1648	2192	1463	1699	1540	2700	985	690	1726	1394	993	757	928	2165	1676	2486	640	750	1832	1267	1514
ENSG00000223823.1	6	3	1	0	16	9	1	3	3	1	0	3	1	4	8	4	8	4	4	4	16	19	81	48	8	15	9	27	6	34
ENSG00000207730.1	0	0	1	2	2	3	0	1	0	1	0	0	2	1	5	0	1	1	0	1	3	0	1	0	2	1	3	0	0	0
ENSG00000207607.1	0	1	0	2	1	1	5	2	2	1	0	0	1	1	0	0	0	1	0	1	1	0	4	0	0	0	0	1	0	2
ENSG00000198976.1	1	0	2	1	1	4	1	0	2	0	1	1	2	7	1	0	1	4	1	0	2	1	2	1	4	1	0	1	0	0
ENSG00000272141.1	338	218	330	544	461	829	613	281	217	552	194	128	511	411	562	162	108	691	493	156	478	333	501	283	450	55	305	158	78	210
ENSG00000205231.1	10	6	8	8	25	10	12	7	3	20	7	2	8	9	19	8	10	22	10	8	19	12	23	12	26	1	9	20	2	38
ENSG00000162571.9	47	14	31	51	75	45	24	36	30	192	61	33	16	20	63	69	14	42	30	31	48	24	51	38	55	3	19	36	12	70
ENSG00000186891.9	32	11	41	23	37	263	14	124	31	28	114	600	22	29	197	39	23	204	66	138	154	127	1312	528	687	270	9	566	98	377
ENSG00000186827.6	366	329	308	362	295	419	83	201	244	252	448	191	95	175	690	120	71	338	407	239	284	219	2053	1042	876	328	138	382	174	549
ENSG00000078808.12	6325	11415	7244	6681	8001	16069	7918	6605	9729	10872	10761	7149	10552	8896	8649	6452	4655	9425	9384	7007	5031	5497	11858	10105	10908	10329	7330	7251	8946	7627
ENSG00000176022.3	767	1634	959	938	1476	1659	840	513	1468	1347	1430	570	1432	1360	661	761	636	1098	1576	817	499	554	1531	1257	1487	1299	623	1014	1271	1491
ENSG00000184163.3	79	44	46	40	76	94	65	50	62	57	194	81	66	69	55	18	16	52	34	83	42	44	50	37	85	41	34	48	32	73
ENSG00000260179.1	24	25	4	19	77	53	24	19	20	25	56	35	46	19	22	23	127	56	27	10	29	43	28	25	27	17	25	13	8	30
ENSG00000160087.16	2038	3378	1713	2236	2740	8086	2342	2341	2989	3222	3355	2407	3557	2605	3422	1696	1484	4060	2864	1664	2342	2287	4604	3685	3637	2710	2202	3297	2186	3400
ENSG00000230415.1	83	48	102	50	68	113	67	48	82	127	32	49	95	94	63	53	30	117	56	40	143	57	220	144	198	60	186	76	53	74
ENSG00000162572.15	1044	332	1193	581	677	2708	772	689	948	1382	265	469	755	1004	1277	526	254	1160	746	826	1617	785	2589	1535	2849	575	1515	918	720	1053
ENSG00000131584.14	6325	3683	5951	3606	4910	9622	3839	5792	3677	6961	2875	3224	7823	5214	5451	3173	2542	4972	5452	4347	3471	4136	8329	9033	8497	3493	2594	5850	4125	5342
ENSG00000169972.7	412	448	350	409	509	947	331	344	439	675	382	328	639	501	750	351	207	811	633	251	267	307	693	664	575	473	278	503	360	747
ENSG00000127054.14	8580	6876	8249	6986	7672	18996	7345	9752	7067	11663	8356	6811	10109	8198	17346	6006	4096	12994	7372	5965	8423	8452	15686	12536	14403	5409	11132	9282	6396	10527
ENSG00000240731.1	305	222	251	282	359	715	267	349	314	466	269	292	356	359	683	269	234	526	343	180	349	311	562	453	422	174	552	253	187	459
ENSG00000224051.2	1224	1655	1574	1198	1578	3155	1159	954	1692	1879	1391	1145	1912	1683	2324	1074	1152	1634	1337	1230	1101	1107	2464	2313	3042	1785	1227	2174	1566	2596
ENSG00000169962.4	103	131	88	73	80	660	115	192	116	112	82	157	99	107	223	63	36	232	100	84	170	241	1481	710	374	391	122	733	112	441
ENSG00000107404.13	5411	4415	5534	4810	4774	17137	4592	5723	4993	6692	5775	5918	7387	5839	9026	3745	3082	8265	6086	3969	3984	4702	7338	8266	8374	3795	5249	5436	4778	6645
ENSG00000162576.12	9211	8502	9092	10644	8504	10171	6366	8490	11198	15906	5771	7876	11217	6591	8388	10148	3659	10514	9340	11482	6480	5189	8207	10450	9912	5679	6604	4820	9702	2971
ENSG00000175756.9	2879	4431	3369	2509	3735	6832	2855	2900	3132	3830	5132	2688	4287	3633	2946	2111	1685	3523	4423	1996	2182	2241	4725	3764	4650	3231	2088	3626	3545	3826
ENSG00000223663.2	3	12	5	4	5	20	7	6	0	3	6	1	6	3	3	3	4	2	8	0	0	5	6	0	2	0	8	3	1	4

Tabla 4: tabla que muestra los 100 primeros genes de la matriz cruda filtrada.

Transformación vst

Préviamente al control de calidad, se ha realizado una transformación vst con el objetivo de estabilizar la varianza, reducir el sesgo y normalizar los datos. Podemos visualizar parte del resultado de esta transformación analizando el contenido de la Tabla 5, que contiene los 100 primeros genes de la matriz de counts normalizada.

	NIT_1	NIT_2	NIT_3	NIT_4	NIT_5	NIT_6	NIT_7	NIT_8	NIT_9	NIT_10	SFI_1	SFI_2	SFI_3	SFI_4	SFI_5	SFI_6	SFI_7	SFI_8	SFI_9	SFI_10	ELI_1	ELI_2	ELI_3	ELI_4	ELI_5	ELI_6	ELI_7	ELI_8	ELI_9	ELI_10
ENSG00000223972.4	4.214794	5.094837	4.720677	4.749960	5.091288	4.214794	4.983472	4.579396	4.777543	4.737504	4.805028	4.747693	4.971263	4.714860	4.693056	4.736153	5.396492	4.908645	5.237513	4.607337	4.214794	4.214794	4.484441	4.214794	4.777859	4.756698	4.914162	4.798252	4.531836	4.714171
ENSG00000227232.4	9.477658	8.796351	10.054278	9.325032	9.224970	9.629893	10.192608	10.154428	9.048699	9.048079	9.021579	9.198377	9.213594	9.106962	10.236705	9.318384	8.901915	9.310563	9.345618	9.998614	10.075999	9.989575	9.957695	9.760677	9.944949	9.222075	8.881376	10.422059	9.520491	9.588688
ENSG00000243485.2	4.583370	4.884380	4.573419	4.594292	4.911636	4.453179	4.214794	4.214794	4.675238	4.517678	4.214794	4.214794	4.834767	4.569275	4.491760	4.736153	5.014522	4.214794	4.562045	4.768248	4.588082	4.578695	4.484441	4.519077	4.497664	4.214794	4.530005	4.553178	4.662265	4.714171
ENSG00000237613.2	4.734641	4.690368	4.214794	4.214794	4.658067	4.214794	4.214794	4.214794	4.541065	4.214794	4.557144	4.214794	4.752726	4.714860	4.491760	4.214794	4.783859	4.500329	4.562045	4.214794	4.588082	4.214794	4.214794	4.214794	4.214794	4.214794	4.758617	4.214794	4.214794	4.623207
ENSG00000268020.2	4.583370	4.214794	4.573419	4.214794	4.658067	4.214794	4.214794	4.214794	4.541065	4.817287	4.697827	4.214794	4.526564	4.214794	4.214794	4.214794	4.783859	4.214794	4.562045	4.214794	4.214794	4.214794	4.214794	4.214794	4.614196	4.756698	4.659692	4.214794	4.214794	4.857385
ENSG00000240361.1	4.583370	4.214794	4.214794	4.594292	4.756638	4.551540	4.761507	4.214794	4.777543	4.214794	4.214794	4.214794	4.752726	4.714860	4.214794	4.214794	4.214794	4.783115	4.214794	4.214794	4.214794	4.578695	4.484441	4.519077	4.497664	4.599098	4.530005	4.553178	4.214794	5.023712
ENSG00000186092.4	4.583370	4.214794	4.720677	4.594292	4.839259	4.551540	4.761507	4.579396	4.675238	4.214794	4.557144	4.214794	4.526564	4.825743	4.214794	4.584448	4.783859	4.849189	4.562045	4.607337	4.214794	4.578695	4.595581	4.214794	4.614196	4.214794	4.758617	4.214794	4.531836	4.714171
ENSG00000238009.2	5.030297	5.031305	5.008714	5.267746	4.839259	5.398246	5.223084	5.660797	5.124452	5.110652	5.108342	5.324147	4.906642	5.258034	4.830379	5.177520	5.456815	5.187029	4.984002	5.803809	5.116941	5.339874	5.798678	5.364775	4.777859	5.773200	5.039162	4.964708	5.200123	4.790480
ENSG00000233750.3	5.406388	5.520950	5.599252	5.674145	7.163805	5.758706	6.067788	5.736728	5.404218	5.669571	5.372222	5.324147	5.428218	5.501414	5.475386	4.948202	7.160013	5.395009	5.476620	4.768248	5.116941	5.805075	5.495267	5.500610	5.006192	5.142843	6.946443	5.098258	4.662265	6.556828
ENSG00000237683.5	8.760188	9.633223	10.383171	9.489792	10.314721	10.062504	9.533344	9.974581	7.508764	9.979255	8.362762	9.824483	8.634970	9.394884	10.795880	9.478276	9.998727	9.544402	9.704728	9.538160	9.211508	10.036026	10.399817	9.065005	9.338658	8.867750	8.971220	10.227047	9.125982	8.751792
ENSG00000268903.1	4.583370	4.551833	5.082374	4.594292	4.658067	4.841286	4.761507	4.729065	4.541065	4.737504	4.697827	4.592675	4.214794	4.999715	5.035842	4.736153	5.014522	4.214794	4.562045	4.992841	4.741251	5.094822	5.170845	4.644325	4.956210	4.599098	4.659692	4.887016	4.531836	4.504066
ENSG00000239906.1	4.214794	5.260021	5.324247	4.967416	5.321999	5.233761	5.289735	4.729065	4.214794	5.910636	5.108342	5.263424	4.834767	5.311951	6.507974	5.032632	5.332178	5.455264	5.290460	5.302553	4.741251	5.618258	5.520020	5.850277	5.353198	4.976788	4.758617	4.692257	4.845128	4.857385
ENSG00000241860.2	6.128989	6.530668	6.545637	6.979051	7.293221	6.714131	6.491466	6.331772	6.577757	6.634929	6.241290	7.291415	6.504546	6.427703	6.864856	7.321988	7.680924	6.750034	6.732255	7.037113	6.374792	7.194004	7.344515	6.829037	6.658800	6.451866	7.631226	6.322563	6.579792	6.911833
ENSG00000222623.1	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.500329	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794
ENSG00000241599.1	4.214794	4.690368	4.214794	4.214794	4.528849	4.214794	4.602528	4.214794	4.675238	4.517678	4.557144	4.214794	4.526564	4.214794	4.766213	4.584448	4.618479	4.783115	4.562045	4.607337	4.214794	4.214794	4.214794	4.214794	4.214794	4.599098	4.530005	4.214794	4.531836	4.714171
ENSG00000228463.4	6.839856	6.192688	6.029085	6.178665	7.070341	7.376431	6.491466	6.685658	5.124452	6.420979	5.540293	6.025850	5.497435	6.727804	6.097716	7.241293	5.759898	6.340660	6.483732	5.235171	6.866513	7.240786	6.038254	6.002061	5.981638	6.474542	5.607442	7.009815	4.918161	5.980371
ENSG00000237094.7	6.257348	5.790243	6.735524	5.867092	6.263385	6.398692	6.187563	6.354132	5.587624	6.491612	6.153024	5.381153	5.736135	5.954101	6.668270	6.333895	5.998608	5.978357	6.004393	6.924090	6.328213	6.681782	6.290406	6.080958	6.296126	5.602823	6.892130	5.525852	5.246306	6.053106
ENSG00000250575.1	4.583370	4.884380	4.720677	4.594292	4.528849	4.795453	4.214794	4.938333	4.863255	4.517678	4.557144	4.964262	4.526564	4.825743	4.693056	4.736153	4.909548	4.908645	5.120791	4.607337	4.588082	5.094822	4.814298	4.953421	4.902267	4.214794	4.659692	4.692257	4.531836	4.623207
ENSG00000233653.3	5.105843	4.961779	4.832815	5.267746	5.436649	4.923613	5.071750	4.729065	5.227814	5.007607	5.043889	5.050448	5.030363	4.825743	4.888132	4.851623	5.332178	5.060631	5.120791	5.082136	4.741251	5.225966	4.922145	4.820040	4.956210	4.756698	5.325900	4.553178	4.918161	5.344719
ENSG00000235249.1	4.214794	4.795954	4.832815	4.214794	4.658067	4.453179	4.214794	4.579396	4.541065	4.517678	4.697827	4.592675	4.214794	4.714860	4.605886	4.214794	4.909548	4.707761	4.704710	4.607337	4.214794	4.578695	4.680492	4.214794	4.214794	4.214794	4.914162	4.214794	4.531836	4.714171
ENSG00000269732.1	4.214794	4.551833	4.573419	4.214794	4.214794	4.214794	4.214794	4.729065	4.214794	4.214794	4.214794	4.592675	4.214794	4.214794	4.491760	4.214794	4.214794	4.214794	4.562045	4.214794	4.214794	4.578695	4.214794	4.214794	4.777859	4.214794	4.530005	4.214794	4.214794	4.214794
ENSG00000256186.1	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.541065	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794
ENSG00000236601.1	4.583370	4.551833	4.573419	4.214794	4.528849	4.453179	4.214794	4.214794	4.214794	4.214794	4.557144	4.592675	4.526564	4.214794	4.605886	4.214794	4.783859	4.500329	4.562045	4.214794	4.214794	4.214794	4.214794	4.519077	4.497664	4.599098	4.214794	4.214794	4.214794	4.504066
ENSG00000236743.1	4.583370	4.551833	4.573419	4.214794	5.142741	4.214794	4.214794	4.729065	4.675238	4.214794	4.805028	4.214794	4.752726	4.214794	4.605886	4.736153	5.014522	4.707761	4.813400	4.214794	4.741251	4.578695	4.214794	4.214794	4.614196	4.214794	4.758617	4.553178	4.214794	4.504066
ENSG00000236679.2	4.214794	4.551833	4.573419	4.214794	5.036207	4.551540	4.602528	4.579396	4.863255	4.214794	4.894789	4.747693	4.906642	4.825743	4.605886	4.851623	6.984188	4.617948	4.562045	4.607337	4.214794	4.214794	4.214794	4.519077	4.497664	4.214794	5.039162	4.553178	4.761750	4.972673
ENSG00000231709.1	4.214794	4.214794	4.832815	4.214794	5.142741	4.551540	4.602528	4.729065	4.541065	4.214794	4.697827	4.747693	4.971263	4.214794	4.830379	4.851623	5.106164	4.908645	5.290460	4.214794	4.588082	4.936962	4.595581	5.206233	4.902267	4.756698	4.659692	4.553178	4.662265	4.504066
ENSG00000235146.2	4.583370	4.690368	4.720677	4.749960	4.756638	4.214794	4.761507	4.729065	4.541065	4.214794	4.557144	4.214794	4.526564	4.569275	4.214794	4.214794	4.214794	4.214794	4.704710	4.607337	4.588082	4.214794	4.484441	4.214794	4.614196	4.214794	4.659692	5.635102	4.214794	4.917581
ENSG00000239664.2	4.849785	4.214794	4.720677	4.594292	4.658067	4.453179	4.602528	4.729065	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.605886	4.214794	4.783859	4.617948	4.562045	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	5.212286	4.214794	4.857385
ENSG00000230021.3	4.583370	4.214794	4.720677	4.749960	5.142741	4.841286	4.761507	5.021681	4.541065	4.817287	4.805028	4.747693	4.906642	4.569275	4.830379	4.851623	4.909548	5.060631	4.813400	4.768248	5.186695	4.841814	4.595581	4.953421	4.614196	4.976788	5.325900	5.312956	4.214794	4.857385
ENSG00000223659.1	4.583370	4.551833	4.214794	4.214794	4.528849	4.214794	4.214794	4.214794	4.675238	4.517678	4.557144	4.592675	4.214794	4.569275	4.605886	4.584448	4.214794	4.617948	4.704710	4.214794	4.214794	4.214794	4.214794	4.214794	4.614196	4.214794	4.914162	4.214794	4.214794	4.504066
ENSG00000225972.1	7.110819	6.977566	6.388306	6.405309	7.978438	6.019011	14.847394	7.047645	6.678662	6.449687	7.115331	6.686142	7.268327	14.324590	6.793271	6.566603	8.347939	6.083417	6.929154	6.396116	6.203837	6.629000	6.068910	11.934969	6.084555	6.021584	7.251206	5.765598	6.025879	8.145157
ENSG00000225630.1	13.573812	14.394469	14.841906	14.170367	13.512986	12.228907	13.248296	14.162501	13.834435	13.266634	13.771371	13.227097	14.268582	13.583045	13.234917	12.911856	13.924769	13.420702	15.189986	13.241105	13.604490	14.393531	13.027993	12.781930	14.247431	13.306156	13.412587	13.133088	13.198275	15.557291
ENSG00000237973.1	9.916680	11.056683	9.084291	11.196149	11.735864	8.411493	14.139627	10.883073	11.706408	9.317166	9.376849	9.742666	11.730180	13.277151	9.261831	10.560557	12.238104	11.734887	11.394388	9.012450	11.580956	10.434323	8.452742	7.205108	10.881666	10.135684	10.009637	8.151112	7.934326	12.213692
ENSG00000229344.1	8.133597	8.487419	7.766708	8.033241	9.246132	6.981635	9.156985	8.445117	8.462734	7.561643	8.296596	7.676465	9.066584	7.951631	8.196647	8.141020	8.979355	8.069529	8.043927	7.769098	7.410406	7.825482	7.143534	6.704637	7.547777	7.243137	9.266615	7.021497	7.203008	9.119827
ENSG00000240409.1	7.136486	7.342230	6.702928	6.516042	7.127169	5.480942	7.594108	7.233592	6.562702	6.014861	6.492432	6.143568	7.260036	7.226468	7.308565	6.747827	7.050729	6.566784	6.848211	6.088145	6.065936	6.024481	5.469901	5.364775	9.371811	5.732980	6.764482	5.563531	6.003987	7.453168
ENSG00000248527.1	15.581600	16.004069	14.659256	15.748015	15.687713	12.911923	15.667349	15.641238	15.045878	15.323015	15.156599	14.643923	16.057768	15.762307	14.159314	14.952034	15.684596	15.433997	15.281203	13.403136	15.323905	15.443441	14.446425	14.318161	15.254245	14.885761	14.835589	13.956681	14.412594	15.617534
ENSG00000198744.5	8.375941	8.270789	8.119421	7.874529	14.097841	6.797982	9.028529	8.493777	8.163763	7.723106	8.600564	8.064738	9.533209	7.918228	8.945248	8.318318	9.618261	8.081293	8.357317	7.403183	7.768638	7.473444	7.266312	6.080958	7.931442	6.991004	9.277010	6.808033	7.851872	9.488384
ENSG00000268663.1	4.214794	4.214794	4.573419	4.594292	4.528849	4.453179	4.602528	4.214794	4.675238	4.214794	4.557144	4.592675	4.526564	4.214794	4.214794	4.851623	4.618479	4.214794	4.214794	4.768248	4.214794	4.214794	4.214794	4.519077	4.214794	4.599098	4.214794	4.214794	4.531836	4.214794
ENSG00000185097.2	4.583370	4.214794	4.214794	4.214794	4.528849	4.214794	4.761507	4.579396	4.675238	4.214794	4.557144	4.592675	4.214794	4.714860	4.605886	4.214794	4.618479	4.500329	4.562045	4.214794	4.214794	4.578695	4.484441	4.214794	4.497664	4.214794	4.214794	4.553178	4.214794	4.623207
ENSG00000229376.3	5.675421	5.819770	5.375707	5.328697	6.032040	5.727595	6.243440	5.807877	5.404218	5.614495	5.223577	5.050448	5.813873	5.139131	5.419975	5.638926	5.885269	5.512106	5.633726	5.082136	5.609606	5.696766	5.205602	5.531893	5.320801	6.021584	6.016564	4.964708	5.332074	5.555636
ENSG00000224956.5	9.043192	7.498331	8.840768	8.391955	8.150551	8.004682	8.576125	8.814075	7.583120	8.638535	8.784005	8.461967	8.140975	5.258034	9.083272	8.147298	7.233140	8.462975	8.217096	8.540427	8.263427	8.430169	7.972107	8.083873	9.023976	7.698907	7.843244	7.881342	7.776334	8.118067
ENSG00000235373.1	5.675421	5.790243	6.001046	5.539961	5.921237	5.283829	5.969689	5.579228	5.443644	5.772146	5.900354	5.625616	5.788542	5.457347	5.298686	5.300956	5.885269	5.779865	6.130289	5.302553	5.251134	5.391986	5.657447	5.702427	5.287235	5.280583	6.100103	5.312956	5.704086	5.798582
ENSG00000223181.1	4.214794	4.551833	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.491760	4.214794	4.214794	4.214794	4.214794	4.214794	4.741251	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.504066
ENSG00000240618.1	5.406388	4.795954	5.942951	5.131550	4.214794	4.551540	4.761507	4.214794	5.067404	5.007607	4.973341	4.592675	5.085074	4.569275	5.298686	4.214794	5.396492	5.060631	5.237513	4.214794	4.741251	5.094822	5.205602	4.739902	4.843340	4.214794	5.146056	4.692257	4.761750	4.857385
ENSG00000229905.1	4.214794	4.214794	4.214794	4.749960	4.658067	4.214794	4.983472	4.214794	4.214794	4.517678	4.557144	4.214794	4.214794	4.569275	4.491760	4.214794	4.909548	4.500329	4.214794	4.607337	4.588082	4.214794	4.484441	4.214794	4.214794	4.214794	4.214794	4.553178	4.214794	4.504066
ENSG00000228327.2	6.931304	7.237536	7.296409	7.809094	7.404102	6.102327	7.197514	6.893469	6.692479	7.350222	7.706136	6.984845	7.025132	7.402360	6.989779	7.023407	7.001125	7.149544	7.649673	6.800949	7.002300	7.817857	7.902800	7.628583	6.891625	7.255892	7.318025	6.262537	6.948123	7.606670
ENSG00000237491.4	7.246481	7.227619	7.241682	7.621459	8.258948	7.138421	7.583903	6.596410	6.592645	7.728747	7.661550	6.793129	7.551855	7.699467	7.650027	7.241293	8.012517	7.251357	8.119115	6.940814	8.392884	7.863007	8.818352	8.320135	7.187573	7.478540	7.049050	8.053721	6.847679	7.952565
ENSG00000230092.3	5.456381	5.399226	5.424552	5.674145	5.799085	5.207620	5.071750	5.021681	4.938308	5.201828	5.275863	5.534649	5.497435	5.767314	6.128548	5.718411	5.106164	5.296925	6.177291	5.676477	5.770050	5.339874	6.543690	5.620518	5.052926	5.773200	5.325900	5.599913	5.332074	6.070636
ENSG00000269831.1	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.602528	4.579396	4.214794	4.214794	4.214794	4.214794	4.526564	4.214794	4.491760	4.851623	4.214794	4.500329	4.562045	4.214794	4.588082	4.578695	4.484441	4.519077	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794
ENSG00000177757.1	5.456381	6.213971	5.676857	6.205917	6.209401	5.557411	6.535908	5.164753	5.932074	6.014861	6.776500	5.895599	6.490031	5.982566	5.448064	5.718411	6.422891	6.148809	6.571794	6.208905	6.065936	5.904090	6.423147	6.042142	5.252383	6.474542	5.724195	6.087104	5.517849	6.418497
ENSG00000225880.4	8.637282	8.038088	8.483605	7.906153	7.717067	8.666077	8.858363	8.599803	7.203008	8.514090	8.627700	8.008137	8.086321	8.342091	9.059310	8.029851	7.617280	8.116017	8.253459	8.457481	8.877080	9.035110	9.873120	9.630849	8.914603	8.064979	8.441382	9.110355	7.571249	7.376269
ENSG00000228794.4	10.479037	10.557424	10.297167	10.452777	10.517903	10.042478	10.443915	10.711076	10.118564	10.183680	11.199887	10.803390	10.763189	10.340400	10.411246	9.987163	10.302810	9.891289	10.301037	10.319211	9.751198	10.303472	9.960525	10.506427	10.189347	9.813118	9.610238	9.747794	10.437238	10.669422
ENSG00000230368.2	5.174798	4.551833	4.573419	4.749960	5.236941	4.883806	4.761507	5.227848	4.777543	4.642357	4.805028	4.592675	4.906642	4.825743	5.231524	5.177520	4.783859	4.707761	4.984002	4.890602	5.040505	5.094822	4.214794	6.339228	5.096933	4.214794	4.758617	4.214794	4.845128	5.071424
ENSG00000234711.1	4.214794	4.884380	4.573419	4.214794	4.756638	4.689957	5.071750	4.729065	4.863255	4.214794	4.557144	4.214794	4.752726	4.825743	4.491760	4.851623	4.783859	4.707761	4.562045	5.082136	4.588082	4.841814	4.595581	5.826917	4.614196	4.214794	4.979455	6.322563	4.214794	4.790480
ENSG00000269308.1	4.214794	4.214794	4.214794	4.214794	4.658067	4.214794	4.214794	4.214794	4.541065	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.588082	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794
ENSG00000272438.1	5.030297	4.551833	4.832815	4.214794	5.091288	5.180660	4.882418	5.772856	5.177720	5.060875	4.805028	4.592675	5.085074	4.714860	4.941010	4.948202	4.909548	4.783115	4.813400	4.768248	4.588082	4.578695	5.544195	5.011193	5.414869	4.756698	4.979455	4.798252	4.761750	4.623207
ENSG00000230699.2	5.985943	5.094837	6.388306	5.385913	6.629747	6.512342	6.243440	6.878559	6.896358	5.696108	5.812923	5.787599	6.383691	6.165239	5.158775	6.020612	6.343060	6.132779	5.237513	5.803809	5.420877	5.965784	6.554124	10.218867	6.253658	5.955732	6.120138	6.155780	5.812838	5.754038
ENSG00000223764.2	7.894624	7.257162	8.455363	7.393950	8.190526	6.981635	8.243943	7.768012	8.079412	7.883305	6.343693	7.481426	7.970311	7.958219	6.746545	7.287972	7.302634	7.806511	7.066232	8.985109	6.733377	7.095458	8.108226	8.342490	7.431600	7.572871	6.752263	7.735079	7.598566	7.508210
ENSG00000187634.6	8.846884	8.340647	8.515866	8.082452	9.262840	10.724012	8.986877	9.508161	10.217826	8.909351	6.560958	8.419287	9.335348	8.696513	7.118925	8.399365	7.670513	9.246083	8.119115	10.089359	7.918723	8.374294	8.676179	9.624798	8.631111	9.244337	7.472371	9.405172	8.507459	9.450247
ENSG00000268179.1	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.592675	4.214794	4.214794	4.214794	4.214794	4.214794	4.617948	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794	4.214794
ENSG00000188976.6	11.902362	12.304945	11.853743	12.064551	12.023240	11.954736	11.958447	11.927504	11.742597	12.119004	12.506859	11.740085	11.980687	11.915595	11.776906	11.961296	11.830805	11.729006	12.163967	11.721126	11.820193	11.731037	11.712041	11.805282	12.116523	12.031198	11.486231	12.121185	11.656762	11.934707
ENSG00000187961.9	10.140389	9.322597	10.054278	10.292521	9.107302	10.918750	10.215716	10.339757	9.712242	9.652407	9.421770	9.513892	10.248443	9.978877	10.473181	9.362070	9.773537	9.660891	9.678311	9.882867	10.814435	10.553144	10.644630	11.053531	10.334869	10.366167	9.978149	10.612851	9.244333	10.492427
ENSG00000187583.6	6.617794	6.353808	6.233165	6.731442	6.332005	6.784361	6.811563	8.450058	6.562702	5.910636	9.003952	7.470931	6.654584	7.215401	7.916764	6.078556	5.667963	7.179398	6.805874	7.693399	7.190158	7.463662	8.767481	8.169820	7.852683	7.726469	6.481301	8.693321	6.621469	7.703963
ENSG00000187642.5	5.751995	5.982874	5.515591	5.902106	5.773039	6.469780	6.067788	7.137515	5.227814	5.585871	7.092890	6.507843	5.886722	5.895067	6.574413	5.862367	5.759898	6.312947	6.030621	7.141609	5.732047	6.765419	7.407450	6.818186	6.770470	6.561556	5.696141	7.790021	6.621469	6.893323
ENSG00000272512.1	8.727320	6.916677	7.662960	8.033241	6.732448	7.925028	8.191429	9.683747	6.198784	7.065633	7.599833	7.934076	6.995286	6.743534	6.449950	5.718411	8.301697	7.171995	7.951950	8.556456	6.304282	6.947420	7.407450	7.843228	7.745259	6.381393	6.582482	7.165045	7.220810	7.755266
ENSG00000188290.6	10.073420	8.631739	9.769660	8.996396	7.942420	8.807208	9.794673	11.004434	8.314542	9.508422	9.716700	9.907692	8.543464	8.429811	8.310611	8.134715	7.809751	8.977894	9.513028	10.042809	8.602789	8.003945	8.263490	8.493252	8.485566	8.542501	7.571171	8.887458	9.207421	8.529511
ENSG00000231702.2	4.583370	4.884380	4.573419	4.967416	4.528849	5.180660	4.602528	4.579396	4.541065	4.517678	4.973341	4.747693	5.030363	4.714860	4.693056	4.584448	5.014522	4.500329	4.562045	4.992841	5.609606	4.841814	4.814298	4.644325	4.497664	4.976788	5.724195	4.214794	4.662265	4.917581
ENSG00000224969.1	5.030297	4.884380	5.149630	4.594292	4.839259	6.136391	4.983472	5.772856	4.541065	4.737504	4.557144	5.381153	5.184272	4.714860	4.605886	4.736153	4.783859	4.617948	4.704710	4.992841	5.471410	5.162980	5.096622	4.953421	4.902267	4.756698	5.829953	4.887016	4.531836	5.274949
ENSG00000187608.5	9.616345	9.301786	10.267770	8.714652	9.216417	9.527266	9.156985	11.910178	9.620778	9.359310	12.506859	9.359134	9.261491	9.708506	8.410346	9.617685	8.182757	9.649132	9.614056	10.217268	9.863920	9.041635	9.710049	10.456218	10.226912	9.975825	8.452451	10.123323	9.918472	9.150608
ENSG00000188157.9	13.959853	14.144854	13.937649	14.220352	13.449465	14.317682	14.188301	14.026667	13.685630	13.698257	14.357766	14.583620	14.009483	14.375416	13.847822	13.530890	13.369722	13.673672	14.354181	13.640560	13.737991	13.887505	13.127731	14.146029	14.059080	13.644379	13.917224	13.419171	13.946929	12.994403
ENSG00000217801.5	7.988118	6.056828	7.967372	7.359877	7.060640	6.993441	7.653843	7.428339	7.597534	7.567963	6.804672	6.984845	6.561073	6.946606	7.713248	7.450377	6.762785	7.258354	7.066232	7.506683	8.929883	7.771228	8.452742	7.375516	8.402269	7.217270	7.903841	8.417606	7.306577	7.395891
ENSG00000273443.1	4.849785	4.690368	4.926649	4.214794	4.911636	5.030611	4.602528	5.660797	4.938308	4.642357	5.108342	4.592675	4.752726	4.569275	5.119880	5.032632	4.783859	5.060631	5.181171	4.214794	4.214794	4.214794	5.096622	5.064689	5.052926	4.214794	5.094431	4.692257	4.214794	4.857385
ENSG00000237330.2	4.849785	4.884380	4.832815	4.594292	5.280468	4.745450	5.351840	5.341949	5.067404	4.887204	4.894789	5.050448	5.030363	4.825743	4.888132	5.108383	5.456815	4.908645	4.904389	4.607337	4.955299	4.214794	4.595581	4.953421	5.006192	4.214794	5.039162	4.964708	4.662265	5.023712
ENSG00000131591.13	10.997126	9.852523	11.028397	10.681166	10.418025	9.330512	10.634780	10.808297	9.560062	10.441516	11.192135	10.900393	10.566012	10.791182	10.884472	10.281006	10.031381	10.340291	10.592252	10.461892	9.941196	10.153544	10.497205	10.478190	10.827542	9.789534	9.459638	10.904625	10.201611	10.193363
ENSG00000223823.1	5.105843	4.795954	4.573419	4.214794	5.436649	4.923613	4.602528	4.843009	4.777543	4.517678	4.214794	4.865642	4.526564	4.918542	4.990014	4.948202	5.332178	4.783115	4.904389	4.992841	5.651950	5.734031	6.423147	6.173014	5.006192	5.647941	5.146056	5.882674	4.983810	5.820224
ENSG00000207730.1	4.214794	4.214794	4.573419	4.749960	4.658067	4.626758	4.214794	4.579396	4.214794	4.517678	4.214794	4.214794	4.654854	4.569275	4.830379	4.214794	4.618479	4.500329	4.214794	4.607337	4.857817	4.214794	4.484441	4.214794	4.614196	4.599098	4.758617	4.214794	4.214794	4.214794
ENSG00000207607.1	4.214794	4.551833	4.214794	4.749960	4.528849	4.453179	5.071750	4.729065	4.675238	4.517678	4.214794	4.214794	4.526564	4.569275	4.214794	4.214794	4.214794	4.500329	4.214794	4.607337	4.588082	4.214794	4.751768	4.214794	4.214794	4.214794	4.214794	4.553178	4.214794	4.623207
ENSG00000198976.1	4.583370	4.214794	4.720677	4.594292	4.528849	4.689957	4.602528	4.214794	4.675238	4.214794	4.557144	4.592675	4.654854	5.139131	4.491760	4.214794	4.618479	4.783115	4.562045	4.214794	4.741251	4.578695	4.595581	4.519077	4.777859	4.599098	4.214794	4.553178	4.214794	4.214794
ENSG00000272141.1	8.808124	8.009729	8.703567	9.530722	8.793135	8.838023	9.754653	8.536203	7.922920	8.936251	7.903880	7.639547	8.910692	8.964372	8.721477	7.871802	7.595414	9.078811	9.153420	7.974671	9.308644	8.754331	8.500298	8.079437	8.485566	6.738845	8.264193	7.625958	6.701139	7.589785
ENSG00000205231.1	5.353700	5.031305	5.211794	5.267746	5.719093	4.961142	5.517299	5.164753	4.777543	5.526201	5.108342	4.747693	5.085074	5.258034	5.391061	5.241397	5.456815	5.512106	5.290460	5.302553	5.770050	5.441442	5.469901	5.248557	5.605042	4.599098	5.146056	5.669189	4.662265	5.902993
ENSG00000162571.9	6.501498	5.441463	6.083315	6.637786	6.643020	5.743257	6.003271	6.238251	5.906979	7.592965	6.610137	6.225126	5.428218	5.733035	6.244843	6.892518	5.667963	5.959933	6.004393	6.237375	6.546150	5.904090	6.022635	5.981516	6.164238	4.876580	5.543988	6.110417	5.290198	6.418497
ENSG00000186891.9	6.155724	5.308771	6.324081	5.936119	6.010673	7.398594	5.614395	7.516461	5.932074	5.747364	7.273031	9.653629	5.623356	6.010378	7.412321	6.333895	6.034146	7.524588	6.717040	7.823339	7.833769	7.540081	9.798114	8.889237	9.045670	8.622488	5.146056	9.270103	6.937318	8.314865
ENSG00000186827.6	8.914124	8.535834	8.612780	8.978002	8.212261	7.958018	7.197514	8.106085	8.069153	7.923147	8.986107	8.132476	6.868992	7.863099	8.994688	7.510437	7.114224	8.142454	8.895928	8.518772	8.612058	8.209808	10.422567	9.814825	9.374929	8.879997	7.301616	8.742637	7.584974	8.806009
ENSG00000078808.12	12.918945	13.509038	13.034743	13.081933	12.794648	13.001807	13.388135	12.949843	13.185524	13.130538	13.469364	13.166869	13.171025	13.296344	12.544545	12.955921	12.741671	12.755483	13.313576	13.248096	12.627137	12.680737	12.920238	13.038732	12.938230	13.744741	12.679552	12.868474	12.982206	12.489321
ENSG00000176022.3	9.923940	10.731669	10.158433	10.286562	10.388850	9.780927	10.192608	9.340393	10.488855	10.159008	10.587933	9.583044	10.325846	10.615810	8.937178	9.921188	9.918073	9.710766	10.765320	10.188478	9.367213	9.440061	10.012351	10.075434	10.105531	10.780236	9.206978	10.073340	10.206018	10.171973
ENSG00000184163.3	7.030845	6.275770	6.429433	6.405309	6.656163	6.333158	6.930927	6.539864	6.532073	6.315228	7.903880	7.112958	6.504546	6.804695	6.128548	5.718411	5.759898	6.132779	6.106112	7.225333	6.419766	6.415408	6.006814	5.960617	6.560014	6.451866	5.949943	6.361087	5.912243	6.457681
ENSG00000260179.1	5.923682	5.819770	4.926649	5.793764	6.669180	5.861399	6.003271	5.736728	5.620735	5.669571	6.527136	6.276732	6.178338	5.697683	5.475386	5.895734	7.790676	6.195712	5.922130	5.424230	6.094760	6.394166	5.590940	5.675795	5.629603	5.732980	5.724195	5.403722	5.099405	5.731096
ENSG00000160087.16	11.299443	11.763204	10.974835	11.514969	11.262978	12.017438	11.642545	11.465637	11.495751	11.390002	11.798292	11.607750	11.613575	11.537224	11.220412	11.046994	11.108909	11.550627	11.613289	11.191444	11.533680	11.426903	11.566141	11.594404	11.367184	11.825302	10.963335	11.739981	10.969473	11.335218
ENSG00000230415.1	7.084670	6.353808	7.252799	6.618248	6.547225	6.503938	6.963210	6.500789	6.810882	7.118726	6.033185	6.590028	6.868992	7.135374	6.244843	6.623576	6.258000	6.902488	6.554642	6.468781	7.743424	6.664417	7.478374	7.269496	7.467468	6.828155	7.650691	6.808033	6.332286	6.470487
ENSG00000162572.15	10.354297	8.547686	10.464334	9.621143	9.309825	10.464458	10.074781	9.745195	9.877945	10.194848	8.296596	9.316249	9.438579	10.189855	9.835052	9.412283	8.672363	9.786663	9.719609	10.203791	11.007278	9.920507	10.749221	10.354807	11.020445	9.641704	10.435820	9.934948	9.419712	9.689026
ENSG00000131584.14	12.918945	11.886645	12.752472	12.197512	12.094914	12.266293	12.349016	12.761294	11.791162	12.490631	11.578036	12.025031	12.741323	12.529324	11.883764	11.938950	11.875317	11.839713	12.533939	12.562677	12.095431	12.273002	12.413510	12.877694	12.579799	12.188177	11.195673	12.560441	11.873048	11.979550
ENSG00000169972.7	9.072912	8.944036	8.781400	9.142266	8.925040	9.015895	8.916005	8.802544	8.829971	9.207078	8.773635	8.834851	9.211475	9.231288	9.106841	8.866132	8.405283	9.295550	9.493676	8.582780	8.531296	8.647071	8.928562	9.197355	8.807817	9.374017	8.146303	9.110355	8.493073	9.219365
ENSG00000127054.14	13.357041	12.780772	13.221400	13.146067	12.734393	13.242218	13.280150	13.509800	12.726490	13.231455	13.105793	13.097282	13.109403	13.178912	13.544050	12.853079	12.558170	13.216639	12.966861	13.016781	13.367220	13.298536	13.322171	13.348507	13.337559	12.815013	13.279594	13.223165	12.500763	12.951666
ENSG00000240731.1	8.672251	8.032461	8.346775	8.646360	8.464753	8.642372	8.631291	8.821711	8.390552	8.711171	8.315814	8.680927	8.434848	8.784084	8.981015	8.515368	8.564721	8.714788	8.669103	8.154321	8.884743	8.664103	8.650663	8.686051	8.402269	8.057786	9.043655	8.207521	7.671081	8.569980
ENSG00000224051.2	10.577825	10.749697	10.855072	10.630313	10.482703	10.679553	10.644543	10.197557	10.688847	10.626079	10.549004	10.554491	10.732511	10.916741	10.672653	10.402282	10.750467	10.263558	10.533482	10.763433	10.464788	10.400490	10.679389	10.932668	11.113387	11.230515	10.140555	11.147193	10.498689	10.952330
ENSG00000169962.4	7.326429	7.396209	7.088471	7.008936	6.707495	8.537515	7.573624	8.048499	7.183899	6.981978	6.911896	7.887720	6.912390	7.280528	7.557559	6.797780	6.422891	7.677734	7.158050	7.238813	7.955725	8.332244	9.966168	9.288243	8.247147	9.115681	7.162931	9.623731	7.081403	8.517736
ENSG00000107404.13	12.694940	12.145840	12.648246	12.610302	12.054737	13.094235	12.605728	12.744096	12.228568	12.434147	12.575508	12.895446	12.659050	12.691688	12.605725	12.175991	12.150730	12.567089	12.691709	12.432273	12.292727	12.456741	12.232075	12.750336	12.558891	12.306900	12.201005	12.455223	12.083116	12.291846
ENSG00000162576.12	13.459072	13.085552	13.361259	13.751539	12.882165	12.345760	13.074601	13.310548	13.387648	13.677603	12.574515	13.306054	13.258852	12.865542	12.500617	13.606845	12.396461	12.912429	13.306820	13.958457	12.990396	12.598031	12.392367	13.086956	12.800776	12.884935	12.529974	12.282925	13.098731	11.143601
ENSG00000175756.9	11.791673	12.151016	11.937577	11.679180	11.704129	11.776678	11.925296	11.770930	11.562331	11.636238	12.406304	11.765261	11.879984	12.012019	11.007923	11.357837	11.289293	11.348654	12.234272	11.450112	11.432906	11.397986	11.603118	11.624645	11.717268	12.076618	10.888092	11.875791	11.656762	11.503225
ENSG00000223663.2	4.849785	5.355075	5.008714	4.967416	4.911636	5.259146	5.223084	5.096476	4.214794	4.737504	5.043889	4.592675	4.971263	4.825743	4.693056	4.851623	5.014522	4.617948	5.181171	4.214794	4.214794	5.020161	4.870592	4.214794	4.614196	4.214794	5.094431	4.798252	4.531836	4.790480

Tabla 6: tabla que muestra los 100 primeros genes de la matriz cruda filtrada y normalizada mediante la transformación vst.

Control de calidad

Ahora que ya disponemos de unos datos con menor sesgo y que están normalizados, ya podemos proseguir con el control de calidad. Tal y como hemos comentado con anterioridad, este control gira principalmente entorno a un análisis gráfico basado la contrucción de un boxplot, un PCA plot y un dendrograma. A continuación se presentan e interpretan conjuntamente los resutados de estas pruebas gráficas. En la Figura 1 se muestran el boxplot y el PCA plot esmentados. En primer lugar, observamos que, tal y como se esperaba, la distribución de pseudocounts inter e intragrupales del boxplot son significativamente homogenéos (Figura 1.A).

Adicionalmente, si nos fijamos en el PCA plot (Figura 1.B), podemos extraer bastante información. Por un lado, identificamos que las dos componentes principales que explican mejor la varianza de las muestras explican un 25.7% (PC1) y un 10.8 % (PC2) de esta. Adicionalmente vemos que -aunque no es perfecta- existe cierta homogeneidad entre las muestras de un mismo grupo. Las muestras del grupo NIT presentan valores negativos y parecidos entre sí para la PC1 mientras que los valores para la PC2 son mucho más variables. Las muestras del grupo SFI presentan valores cercanos a 0 y bastante parecidos entre sí para la PC1 mientras que -análogamente al grupo NIT- los valores para la PC2 difieren significativamente. Finalmente -a excepción de dos muestras (ELI-7 y ELI-9)- todas las muestras del grupo ELI presentan valores positivos y significativamente elevados para la PC1. En cuanto a la PC2, observamos una dispersión parecida a la de los otros grupos pero no tan acentuada. En síntesis, podríamos concluir que -aunque no es muy clara- observamos una segmentación de las muestras por grupos. Los grupos NIT y SFI son bastante parecidos entre ellos, mientras que el grupo ELI es el que está más alejado del resto. Si así nos conviene, podríamos considerar las muestras ELI-7 y ELI-9 como problemáticas y eliminarlas.

Figura 1: boxplot de los pseudocounts (A). PCA plot de los pseudocounts (B).

En la Figura 2 se muestra el dendrograma. Primeramente, podemos identificar que la división óptima implica la construcción de únicamente dos clústers. El primero incluye todas las muestras NIT, 7/10 muestras SFI y 2/10 muestras ELI. En cambio, el segundo no incluye ninguna muestra NIT, e incluye 3/10 muestras SFI y 8/10 muestras ELI. Estos resultados sustentan lo observado en el PCA plot. Esto es -básicamente- que los grupos NIT y SFI son significativamente parecidos entre ellos y -a su vez- considerablemente diferentes al grupo EFI.

Figura 2: dendrograma resultante del análisis de clustering jerarárquico de las 30 muestras.

Selección de genes (DEG)

Una vez los datos han pasado el control de calidad y se han establecido las comparaciones, identificaremos que genes estan diferencialmente expresados en cada una de ellas. A continuación se muestra, para cada una de las 3 comparaciones, una topTable con los 75 genes que parecen presentar una mayor expresión diferencial. Estos son -de los genes que presentan un p-valor ajustado < 0.1- aquellos que presentan valores absolutos más grandes para el log2FC. Adicionalmente, también se muestra un un resumen que contiene -entre otros- el número y el porcentaje de genes up-regulated y down-regulated.

NIT vs SFI:

En primer lugar, vamos a analizar los resultados obtenidos para la comparación NIT vs SFI. Tal y como podemos observar en la Tabla 7, la aplicación de pequeñas infilitraciones focales en el tejido tiroideo (SFI) desencadena una respuesta que implica -almenos- la expresión diferencial de 330 (0.71%) genes respecto a la condición normal (NIT). De estos genes, 51 (0.11%) están sobrexpresados y 279 (0.6%) infraexpresados.

	baseMean	log2FoldChange	lfcSE	stat	pvalue	padj	symbol	entrez
ENSG00000105369	1948.87	-4.90	0.80	-6.14	8.4e-10	4.6e-07	CD79A	973
ENSG00000170476	1628.40	-4.15	0.74	-5.61	2.0e-08	7.4e-06	MZB1	51237
ENSG00000156738	5112.78	-4.50	0.81	-5.54	3.0e-08	1.0e-05	MS4A1	931
ENSG00000181847	505.03	-3.02	0.55	-5.52	3.3e-08	1.1e-05	TIGIT	201633
ENSG00000156234	561.78	-4.44	0.83	-5.32	1.0e-07	3.0e-05	CXCL13	10563
ENSG00000110777	1986.24	-3.24	0.62	-5.19	2.1e-07	5.7e-05	POU2AF1	5450
ENSG00000226777	416.84	-3.91	0.76	-5.13	2.8e-07	7.5e-05	FAM30A	9834
ENSG00000132465	7603.68	-3.78	0.74	-5.09	3.6e-07	9.1e-05	JCHAIN	3512
ENSG00000129204	428.14	2.15	0.44	4.89	1.0e-06	2.4e-04	USP6	9098
ENSG00000187862	90.87	-2.94	0.60	-4.86	1.2e-06	2.7e-04	TTC24	164118
ENSG00000235304	36.49	-5.87	1.24	-4.74	2.1e-06	4.8e-04	LINC01281	286442
ENSG00000048462	108.47	-2.52	0.54	-4.68	2.8e-06	6.3e-04	TNFRSF17	608
ENSG00000163534	804.39	-3.53	0.76	-4.63	3.7e-06	8.2e-04	FCRL1	115350
ENSG00000160856	926.56	-3.03	0.66	-4.57	4.8e-06	1.0e-03	FCRL3	115352
ENSG00000177455	1184.57	-3.51	0.77	-4.56	5.1e-06	1.1e-03	CD19	930
ENSG00000254709	101.05	-4.44	0.98	-4.54	5.6e-06	1.1e-03	IGLL5	100423062
ENSG00000122188	236.81	-2.19	0.49	-4.51	6.6e-06	1.3e-03	LAX1	54900
ENSG00000235532	73.30	-4.17	0.93	-4.51	6.6e-06	1.3e-03	LINC00402	100507612
ENSG00000026751	787.52	-2.25	0.50	-4.49	7.2e-06	1.4e-03	SLAMF7	57823
ENSG00000197057	177.97	-2.42	0.54	-4.45	8.5e-06	1.7e-03	DTHD1	401124
ENSG00000086967	152.58	-3.35	0.76	-4.38	1.2e-05	2.3e-03	MYBPC2	4606
ENSG00000136573	911.22	-2.90	0.66	-4.38	1.2e-05	2.3e-03	BLK	640
ENSG00000083454	913.26	-2.62	0.60	-4.37	1.2e-05	2.3e-03	P2RX5	5026
ENSG00000140465	120.99	-3.68	0.84	-4.36	1.3e-05	2.4e-03	CYP1A1	1543
ENSG00000089012	258.32	-2.24	0.51	-4.36	1.3e-05	2.4e-03	SIRPG	55423
ENSG00000121895	207.04	-2.60	0.60	-4.32	1.5e-05	2.8e-03	TMEM156	80008
ENSG00000196092	398.98	-3.43	0.80	-4.31	1.6e-05	2.8e-03	PAX5	5079
ENSG00000159958	162.27	-3.54	0.82	-4.30	1.7e-05	3.0e-03	TNFRSF13C	115650
ENSG00000122224	497.02	-2.47	0.58	-4.28	1.8e-05	3.2e-03	LY9	4063
ENSG00000143297	1671.07	-3.42	0.80	-4.27	2.0e-05	3.4e-03	FCRL5	83416
ENSG00000113088	259.07	-2.48	0.58	-4.26	2.0e-05	3.4e-03	GZMK	3003
ENSG00000116748	50.56	-2.34	0.55	-4.24	2.2e-05	3.7e-03	AMPD1	270
ENSG00000198576	199.58	2.48	0.59	4.18	2.9e-05	4.7e-03	ARC	23237
ENSG00000086159	5.21	2.72	0.66	4.13	3.6e-05	5.6e-03	AQP6	363
ENSG00000138755	1841.40	-2.50	0.61	-4.13	3.6e-05	5.7e-03	CXCL9	4283
ENSG00000168081	68.51	-2.60	0.64	-4.07	4.7e-05	7.1e-03	PNOC	5368
ENSG00000092345	4.26	4.26	1.07	3.97	7.0e-05	1.0e-02	DAZL	1618
ENSG00000257242	72.86	-2.07	0.52	-3.96	7.5e-05	1.1e-02	LINC01619	256021
ENSG00000240505	194.19	-4.25	1.08	-3.92	8.7e-05	1.2e-02	TNFRSF13B	23495
ENSG00000131096	18.83	2.26	0.58	3.91	9.2e-05	1.3e-02	PYY	5697
ENSG00000165076	9.47	2.28	0.59	3.89	1.0e-04	1.4e-02	PRSS37	136242
ENSG00000225362	35.25	2.07	0.54	3.85	1.2e-04	1.6e-02	CT62	196993
ENSG00000183918	263.35	-2.09	0.54	-3.85	1.2e-04	1.6e-02	SH2D1A	4068
ENSG00000255760	66.56	-4.18	1.09	-3.84	1.2e-04	1.6e-02	LINC02422	105369723
ENSG00000269404	416.45	-2.45	0.64	-3.82	1.3e-04	1.8e-02	SPIB	6689
ENSG00000171903	519.64	-2.20	0.58	-3.80	1.5e-04	1.9e-02	CYP4F11	57834
ENSG00000234184	32.14	-4.48	1.18	-3.79	1.5e-04	2.0e-02	LINC01781	101927412
ENSG00000178562	397.88	-2.24	0.60	-3.76	1.7e-04	2.1e-02	CD28	940
ENSG00000136931	7.75	2.98	0.80	3.73	1.9e-04	2.4e-02	NR5A1	2516
ENSG00000158477	22.99	-3.95	1.07	-3.70	2.2e-04	2.7e-02	CD1A	909
ENSG00000137673	23.60	-2.89	0.78	-3.69	2.2e-04	2.7e-02	MMP7	4316
ENSG00000135248	11.80	2.57	0.70	3.68	2.3e-04	2.8e-02	FAM71F1	84691
ENSG00000102970	22.77	-3.33	0.91	-3.65	2.6e-04	3.1e-02	CCL17	6361
ENSG00000049249	22.64	-2.35	0.65	-3.64	2.8e-04	3.3e-02	TNFRSF9	3604
ENSG00000249923	7.03	2.03	0.56	3.62	3.0e-04	3.5e-02	LOC284865	284865
ENSG00000255733	55.44	-2.68	0.75	-3.55	3.9e-04	4.4e-02	IFNG-AS1	100885789
ENSG00000185972	11.61	2.40	0.68	3.52	4.2e-04	4.7e-02	CCIN	881
ENSG00000163599	420.70	-2.19	0.63	-3.49	4.9e-04	5.4e-02	CTLA4	1493
ENSG00000254211	7.61	-2.54	0.73	-3.47	5.2e-04	5.6e-02	LINC01485	101928154
ENSG00000078589	193.96	-2.04	0.59	-3.47	5.3e-04	5.7e-02	P2RY10	27334
ENSG00000234572	10.73	-3.91	1.14	-3.44	5.8e-04	6.0e-02	LINC01800	101927438
ENSG00000163508	258.50	-2.01	0.58	-3.44	5.9e-04	6.1e-02	EOMES	8320
ENSG00000169245	334.62	-2.56	0.75	-3.43	6.1e-04	6.3e-02	CXCL10	3627
ENSG00000159556	10.15	-2.90	0.85	-3.40	6.7e-04	6.8e-02	ISL2	64843
ENSG00000256574	14.46	-3.47	1.02	-3.39	6.9e-04	6.9e-02	OR13A1	79290
ENSG00000231439	54.87	2.28	0.68	3.34	8.3e-04	8.0e-02	WASIR2	100132169
ENSG00000144460	7.44	-3.25	0.98	-3.33	8.6e-04	8.2e-02	NYAP2	57624
ENSG00000100721	310.88	-3.08	0.93	-3.30	9.6e-04	8.9e-02	TCL1A	8115
ENSG00000204595	1.65	3.59	1.09	3.29	9.9e-04	9.2e-02	DPRX	503834
ENSG00000185155	28.43	-2.44	0.75	-3.27	1.1e-03	9.9e-02	MIXL1	83881

out of 46777 with nonzero total read count
adjusted p-value < 0.1
LFC > 0 (up)       : 51, 0.11%
LFC < 0 (down)     : 279, 0.6%
outliers [1]       : 0, 0%
low counts [2]     : 17235, 37%
(mean count < 2)
[1] see 'cooksCutoff' argument of ?results
[2] see 'independentFiltering' argument of ?results

Tabla 7: toptable y tabla resumen que contienen tanto la lista como el resumen de los genes que presentan evidencia de estar diferencialmente expresados entre las condiciones NIT y SFI.

NIT vs ELI:

A continuación, comentaremos el output obtenido en la comparación NIT vs ELI. Si nos fijamos en la Tabla 8, la aplicación de infilitraciones extensivas en el tejido tiroideo (ELI) desencadena una respuesta que implica -por lo menos- la expresión diferencial de 3814 (8.1%) genes respecto a la condición normal (NIT). De estos genes, un 2% están sobrexpresados y un 6.1% infraexpresados.

	baseMean	log2FoldChange	lfcSE	stat	pvalue	padj	symbol	entrez
ENSG00000048462	108.47	-6.00	0.53	-11.28	1.6e-29	2.6e-25	TNFRSF17	608
ENSG00000156234	561.78	-9.23	0.83	-11.09	1.4e-28	1.6e-24	CXCL13	10563
ENSG00000160856	926.56	-6.91	0.66	-10.46	1.4e-25	4.9e-22	FCRL3	115352
ENSG00000163534	804.39	-7.87	0.76	-10.33	5.2e-25	1.5e-21	FCRL1	115350
ENSG00000196092	398.98	-8.19	0.79	-10.33	5.1e-25	1.5e-21	PAX5	5079
ENSG00000271856	177.49	-6.05	0.59	-10.27	9.4e-25	2.5e-21	LINC01215	101929623
ENSG00000269404	416.45	-6.52	0.64	-10.18	2.4e-24	5.4e-21	SPIB	6689
ENSG00000168081	68.51	-6.38	0.63	-10.16	2.9e-24	6.1e-21	PNOC	5368
ENSG00000177455	1184.57	-7.79	0.77	-10.13	3.9e-24	7.9e-21	CD19	930
ENSG00000100721	310.88	-9.30	0.92	-10.07	7.2e-24	1.3e-20	TCL1A	8115
ENSG00000083454	913.26	-6.02	0.60	-10.08	7.0e-24	1.3e-20	P2RX5	5026
ENSG00000167483	842.93	-6.36	0.64	-10.00	1.6e-23	2.6e-20	NIBAN3	199786
ENSG00000089012	258.32	-5.10	0.51	-9.98	1.8e-23	2.8e-20	SIRPG	55423
ENSG00000105369	1948.87	-7.92	0.80	-9.93	3.2e-23	4.6e-20	CD79A	973
ENSG00000122188	236.81	-4.79	0.48	-9.91	3.7e-23	5.0e-20	LAX1	54900
ENSG00000117322	963.92	-7.51	0.76	-9.83	8.1e-23	1.0e-19	CR2	1380
ENSG00000187862	90.87	-5.81	0.60	-9.71	2.8e-22	3.0e-19	TTC24	164118
ENSG00000136573	911.22	-6.39	0.66	-9.65	5.0e-22	4.8e-19	BLK	640
ENSG00000181847	505.03	-5.24	0.55	-9.59	9.2e-22	8.7e-19	TIGIT	201633
ENSG00000188404	1115.88	-4.32	0.45	-9.56	1.2e-21	1.1e-18	SELL	6402
ENSG00000226777	416.84	-7.22	0.76	-9.51	1.9e-21	1.7e-18	FAM30A	9834
ENSG00000007312	900.45	-4.23	0.44	-9.50	2.1e-21	1.8e-18	CD79B	974
ENSG00000156738	5112.78	-7.69	0.81	-9.48	2.6e-21	2.1e-18	MS4A1	931
ENSG00000245164	881.80	-4.87	0.51	-9.47	2.7e-21	2.2e-18	LINC00861	100130231
ENSG00000162894	1340.03	-4.33	0.46	-9.46	3.1e-21	2.4e-18	FCMR	9214
ENSG00000227507	832.23	-5.23	0.56	-9.40	5.4e-21	4.2e-18	LTB	4050
ENSG00000110777	1986.24	-5.83	0.62	-9.35	8.7e-21	6.5e-18	POU2AF1	5450
ENSG00000009790	1329.73	-4.06	0.44	-9.24	2.6e-20	1.8e-17	TRAF3IP3	80342
ENSG00000241106	566.38	-4.42	0.48	-9.24	2.5e-20	1.8e-17	HLA-DOB	3112
ENSG00000170476	1628.40	-6.82	0.74	-9.23	2.7e-20	1.9e-17	MZB1	51237
ENSG00000104921	387.71	-5.87	0.64	-9.21	3.4e-20	2.3e-17	FCER2	2208
ENSG00000104894	2626.16	-4.10	0.45	-9.15	5.5e-20	3.5e-17	CD37	951
ENSG00000247774	396.41	-3.43	0.38	-8.99	2.4e-19	1.4e-16	PCED1B-AS1	100233209
ENSG00000137265	1005.07	-4.93	0.55	-8.96	3.1e-19	1.7e-16	IRF4	3662
ENSG00000233355	329.66	-5.42	0.61	-8.95	3.5e-19	1.9e-16	CHRM3-AS2	100506915
ENSG00000026751	787.52	-4.47	0.50	-8.92	4.6e-19	2.3e-16	SLAMF7	57823
ENSG00000247982	1586.16	-3.80	0.43	-8.91	5.0e-19	2.5e-16	LINC00926	283663
ENSG00000121895	207.04	-5.31	0.60	-8.85	8.4e-19	4.1e-16	TMEM156	80008
ENSG00000173200	1754.14	-4.39	0.50	-8.80	1.4e-18	6.5e-16	PARP15	165631
ENSG00000170006	359.25	-3.19	0.36	-8.78	1.6e-18	7.1e-16	TMEM154	201799
ENSG00000169442	936.51	-3.97	0.45	-8.75	2.2e-18	9.4e-16	CD52	1043
ENSG00000113088	259.07	-5.05	0.58	-8.70	3.5e-18	1.4e-15	GZMK	3003
ENSG00000162739	801.36	-4.42	0.51	-8.67	4.2e-18	1.7e-15	SLAMF6	114836
ENSG00000159618	310.73	-3.66	0.42	-8.67	4.3e-18	1.7e-15	ADGRG5	221188
ENSG00000128218	146.23	-4.66	0.54	-8.66	4.7e-18	1.8e-15	VPREB3	29802
ENSG00000111913	1438.34	-3.13	0.36	-8.61	7.2e-18	2.8e-15	RIPOR2	9750
ENSG00000137078	178.61	-3.80	0.45	-8.52	1.7e-17	6.0e-15	SIT1	27240
ENSG00000132185	270.99	-7.08	0.84	-8.45	3.0e-17	1.0e-14	FCRLA	84824
ENSG00000205744	1692.35	-2.85	0.34	-8.42	3.9e-17	1.3e-14	DENND1C	79958
ENSG00000198796	140.51	-5.92	0.71	-8.36	6.5e-17	2.1e-14	ALPK2	115701
ENSG00000101057	303.27	-4.65	0.56	-8.35	6.7e-17	2.2e-14	MYBL2	4605
ENSG00000159753	1359.38	-4.25	0.51	-8.33	8.3e-17	2.7e-14	CARMIL2	146206
ENSG00000124256	416.94	-4.50	0.54	-8.31	9.4e-17	3.0e-14	ZBP1	81030
ENSG00000185905	248.61	-4.02	0.48	-8.31	9.9e-17	3.1e-14	C16orf54	283897
ENSG00000174123	468.17	-6.05	0.73	-8.26	1.5e-16	4.5e-14	TLR10	81793
ENSG00000167895	4332.53	-4.08	0.49	-8.26	1.5e-16	4.6e-14	TMC8	147138
ENSG00000178199	404.14	-3.94	0.48	-8.23	1.8e-16	5.5e-14	ZC3H12D	340152
ENSG00000079263	565.58	-4.12	0.50	-8.22	2.0e-16	6.0e-14	SP140	11262
ENSG00000162892	285.12	-4.11	0.50	-8.21	2.1e-16	6.2e-14	IL24	11009
ENSG00000110934	857.69	-2.98	0.36	-8.21	2.3e-16	6.6e-14	BIN2	51411
ENSG00000198286	937.24	-3.64	0.44	-8.19	2.5e-16	7.1e-14	CARD11	84433
ENSG00000143297	1671.07	-6.54	0.80	-8.17	3.0e-16	8.2e-14	FCRL5	83416
ENSG00000158517	297.79	-3.28	0.40	-8.17	3.1e-16	8.3e-14	NCF1	653361
ENSG00000102879	3973.52	-3.46	0.42	-8.15	3.5e-16	9.4e-14	CORO1A	11151
ENSG00000186265	173.55	-4.33	0.53	-8.12	4.6e-16	1.2e-13	BTLA	151888
ENSG00000143851	1011.88	-3.71	0.46	-8.11	5.2e-16	1.3e-13	PTPN7	5778
ENSG00000132704	642.49	-7.26	0.90	-8.10	5.5e-16	1.4e-13	FCRL2	79368
ENSG00000147168	1509.05	-3.66	0.45	-8.10	5.6e-16	1.4e-13	IL2RG	3561
ENSG00000185862	1503.56	-3.67	0.45	-8.09	5.9e-16	1.5e-13	EVI2B	2124
ENSG00000072858	325.17	-3.09	0.38	-8.08	6.3e-16	1.5e-13	SIDT1	54847
ENSG00000175857	189.92	-4.34	0.54	-8.08	6.4e-16	1.6e-13	GAPT	202309
ENSG00000168421	538.54	-3.84	0.48	-8.06	7.6e-16	1.8e-13	RHOH	399
ENSG00000104783	669.15	-4.01	0.50	-8.06	7.6e-16	1.8e-13	KCNN4	3783
ENSG00000165178	161.62	-3.41	0.42	-8.04	9.1e-16	2.1e-13	NCF1C	654817
ENSG00000122122	1299.62	-3.44	0.43	-8.04	9.2e-16	2.2e-13	SASH3	54440
ENSG00000072818	2718.75	-3.38	0.42	-8.02	1.1e-15	2.5e-13	ACAP1	9744
ENSG00000167286	330.56	-3.40	0.43	-8.00	1.3e-15	3.0e-13	CD3D	915
ENSG00000163518	29.59	-8.07	1.01	-7.99	1.4e-15	3.2e-13	FCRL4	83417
ENSG00000117091	569.45	-3.62	0.45	-7.98	1.4e-15	3.2e-13	CD48	962
ENSG00000123329	2274.26	-3.45	0.43	-7.98	1.5e-15	3.4e-13	ARHGAP9	64333
ENSG00000167077	426.96	-3.39	0.43	-7.97	1.6e-15	3.5e-13	MEI1	150365
ENSG00000112303	251.58	-3.28	0.41	-7.95	1.8e-15	4.0e-13	VNN2	8875
ENSG00000128340	714.24	-3.42	0.43	-7.92	2.4e-15	5.2e-13	RAC2	5880
ENSG00000104814	1148.80	-3.57	0.45	-7.91	2.7e-15	5.7e-13	MAP4K1	11184
ENSG00000224137	31.18	-6.81	0.86	-7.90	2.8e-15	5.9e-13	LINC01857	102724714
ENSG00000182866	1148.45	-3.58	0.45	-7.88	3.3e-15	6.8e-13	LCK	3932
ENSG00000254709	101.05	-7.65	0.97	-7.86	3.9e-15	8.0e-13	IGLL5	100423062
ENSG00000010671	576.56	-3.43	0.44	-7.83	5.1e-15	1.0e-12	BTK	695
ENSG00000185155	28.43	-5.71	0.73	-7.81	5.8e-15	1.2e-12	MIXL1	83881
ENSG00000172794	424.15	-3.29	0.42	-7.80	6.0e-15	1.2e-12	RAB37	326624
ENSG00000159958	162.27	-6.40	0.82	-7.80	6.1e-15	1.2e-12	TNFRSF13C	115650
ENSG00000174130	414.53	-3.52	0.45	-7.80	6.4e-15	1.2e-12	TLR6	10333
ENSG00000197057	177.97	-4.21	0.54	-7.76	8.7e-15	1.6e-12	DTHD1	401124
ENSG00000198851	1165.38	-3.33	0.43	-7.73	1.1e-14	2.0e-12	CD3E	916
ENSG00000234184	32.14	-8.97	1.16	-7.72	1.1e-14	2.1e-12	LINC01781	101927412
ENSG00000070190	337.18	-3.99	0.52	-7.70	1.4e-14	2.5e-12	DAPP1	27071
ENSG00000167208	325.76	-3.36	0.44	-7.68	1.6e-14	2.9e-12	SNX20	124460
ENSG00000185811	1556.16	-3.30	0.43	-7.67	1.8e-14	3.1e-12	IKZF1	10320
ENSG00000255733	55.44	-5.72	0.75	-7.66	1.9e-14	3.3e-12	IFNG-AS1	100885789
ENSG00000082293	54.95	-4.33	0.57	-7.64	2.2e-14	3.9e-12	COL19A1	1310
ENSG00000081059	1759.92	-2.44	0.32	-7.63	2.4e-14	4.2e-12	TCF7	6932
ENSG00000136490	2097.08	-3.23	0.42	-7.61	2.7e-14	4.7e-12	LIMD2	80774
ENSG00000145088	149.10	-2.61	0.34	-7.61	2.8e-14	4.9e-12	EAF2	55840
ENSG00000259772	161.19	-3.62	0.48	-7.60	3.0e-14	5.2e-12	LOC283710	283710
ENSG00000132465	7603.68	-5.64	0.74	-7.59	3.2e-14	5.4e-12	JCHAIN	3512
ENSG00000161929	216.32	-3.29	0.43	-7.58	3.5e-14	6.0e-12	SCIMP	388325
ENSG00000182487	188.13	-3.25	0.43	-7.57	3.6e-14	6.0e-12	NCF1B	654816
ENSG00000163599	420.70	-4.74	0.63	-7.57	3.9e-14	6.4e-12	CTLA4	1493
ENSG00000188389	430.46	-3.49	0.46	-7.56	4.2e-14	6.9e-12	PDCD1	5133
ENSG00000076662	1215.60	-2.35	0.31	-7.54	4.7e-14	7.7e-12	ICAM3	3385
ENSG00000220008	92.53	-3.75	0.50	-7.54	4.9e-14	7.9e-12	LINGO3	645191
ENSG00000143119	2802.55	-3.32	0.44	-7.51	5.9e-14	9.5e-12	CD53	963
ENSG00000227039	991.70	-4.34	0.58	-7.50	6.5e-14	1.0e-11	ITGB2-AS1	100505746
ENSG00000166501	1072.68	-3.40	0.45	-7.49	6.7e-14	1.1e-11	PRKCB	5579
ENSG00000213654	1540.42	-2.31	0.31	-7.49	6.8e-14	1.1e-11	GPSM3	63940
ENSG00000005844	2587.91	-3.55	0.48	-7.47	7.9e-14	1.2e-11	ITGAL	3683
ENSG00000188452	404.31	-2.86	0.38	-7.46	8.8e-14	1.4e-11	CERKL	375298
ENSG00000172578	1244.95	-3.61	0.48	-7.45	9.0e-14	1.4e-11	KLHL6	89857
ENSG00000234883	214.70	-3.79	0.51	-7.45	9.1e-14	1.4e-11	MIR155HG	114614
ENSG00000035720	167.93	-5.21	0.70	-7.45	9.2e-14	1.4e-11	STAP1	26228
ENSG00000013725	901.29	-3.68	0.49	-7.45	9.6e-14	1.4e-11	CD6	923
ENSG00000028277	1067.70	-3.54	0.47	-7.45	9.6e-14	1.4e-11	POU2F2	5452
ENSG00000109943	74.47	-3.55	0.48	-7.44	1.0e-13	1.5e-11	CRTAM	56253
ENSG00000235532	73.30	-6.84	0.92	-7.42	1.2e-13	1.7e-11	LINC00402	100507612
ENSG00000163568	230.72	-4.66	0.63	-7.39	1.4e-13	2.1e-11	AIM2	9447
ENSG00000238121	201.28	-3.53	0.48	-7.39	1.4e-13	2.1e-11	LINC00426	100188949
ENSG00000235304	36.49	-9.06	1.23	-7.36	1.8e-13	2.6e-11	LINC01281	286442
ENSG00000129173	41.16	-3.68	0.50	-7.36	1.8e-13	2.7e-11	E2F8	79733
ENSG00000068831	3363.16	-2.89	0.39	-7.36	1.9e-13	2.7e-11	RASGRP2	10235
ENSG00000110665	452.18	-3.61	0.49	-7.35	1.9e-13	2.8e-11	C11orf21	29125
ENSG00000015285	904.07	-2.79	0.38	-7.34	2.1e-13	2.9e-11	WAS	7454
ENSG00000078589	193.96	-4.30	0.59	-7.33	2.4e-13	3.3e-11	P2RY10	27334
ENSG00000134061	253.71	-4.35	0.59	-7.32	2.5e-13	3.5e-11	CD180	4064
ENSG00000188820	94.81	-2.87	0.39	-7.31	2.6e-13	3.7e-11	CALHM6	441168
ENSG00000102096	2309.09	-3.39	0.46	-7.31	2.7e-13	3.7e-11	PIM2	11040
ENSG00000115085	1795.87	-3.35	0.46	-7.29	3.2e-13	4.4e-11	ZAP70	7535
ENSG00000168071	3370.62	-3.11	0.43	-7.26	3.8e-13	5.1e-11	CCDC88B	283234
ENSG00000257242	72.86	-3.77	0.52	-7.25	4.1e-13	5.5e-11	LINC01619	256021
ENSG00000147138	203.08	-3.81	0.53	-7.23	4.7e-13	6.2e-11	GPR174	84636
ENSG00000130475	470.50	-3.52	0.49	-7.22	5.2e-13	6.8e-11	FCHO1	23149
ENSG00000122224	497.02	-4.15	0.57	-7.21	5.4e-13	7.1e-11	LY9	4063
ENSG00000100385	858.70	-3.03	0.42	-7.21	5.5e-13	7.1e-11	IL2RB	3560
ENSG00000170054	54.55	-9.79	1.36	-7.19	6.3e-13	8.1e-11	SERPINA9	327657
ENSG00000270164	213.52	-3.04	0.42	-7.19	6.4e-13	8.1e-11	LINC01480	101927931
ENSG00000160185	255.17	-3.47	0.48	-7.19	6.6e-13	8.3e-11	UBASH3A	53347
ENSG00000204475	66.12	-4.24	0.59	-7.19	6.7e-13	8.4e-11	NCR3	259197
ENSG00000226979	58.88	-3.63	0.50	-7.18	6.8e-13	8.5e-11	LTA	4049
ENSG00000130487	114.08	-4.20	0.58	-7.18	7.0e-13	8.7e-11	KLHDC7B	113730
ENSG00000187912	94.10	-5.82	0.81	-7.17	7.3e-13	9.1e-11	CLEC17A	388512
ENSG00000153283	793.61	-2.36	0.33	-7.16	7.8e-13	9.6e-11	CD96	10225
ENSG00000112486	201.36	-2.52	0.35	-7.14	9.4e-13	1.2e-10	CCR6	1235
ENSG00000183918	263.35	-3.87	0.54	-7.12	1.1e-12	1.3e-10	SH2D1A	4068
ENSG00000175643	135.27	-2.51	0.35	-7.11	1.2e-12	1.4e-10	RMI2	116028
ENSG00000146285	276.03	-3.43	0.48	-7.10	1.2e-12	1.5e-10	SCML4	256380
ENSG00000105122	2533.98	-2.87	0.40	-7.10	1.3e-12	1.5e-10	RASAL3	64926
ENSG00000255760	66.56	-7.66	1.08	-7.09	1.3e-12	1.6e-10	LINC02422	105369723
ENSG00000268041	43.27	-4.37	0.62	-7.09	1.3e-12	1.6e-10	ERFL	390937
ENSG00000184293	66.17	-3.93	0.56	-7.08	1.4e-12	1.7e-10	CLECL1	160365
ENSG00000160654	225.41	-3.39	0.48	-7.08	1.4e-12	1.7e-10	CD3G	917
ENSG00000139193	663.94	-2.78	0.39	-7.08	1.4e-12	1.7e-10	CD27	939
ENSG00000225783	2059.09	-3.17	0.45	-7.07	1.5e-12	1.8e-10	MIAT	440823
ENSG00000106948	4666.65	-2.00	0.28	-7.06	1.7e-12	1.9e-10	AKNA	80709
ENSG00000116852	1167.04	-2.88	0.41	-7.04	1.9e-12	2.2e-10	KIF21B	23046
ENSG00000163508	258.50	-4.10	0.58	-7.04	1.9e-12	2.2e-10	EOMES	8320
ENSG00000138964	1969.45	-2.94	0.42	-7.04	1.9e-12	2.2e-10	PARVG	64098
ENSG00000066294	1082.72	-3.37	0.48	-7.04	2.0e-12	2.2e-10	CD84	8832
ENSG00000117009	83.18	-2.74	0.39	-7.04	2.0e-12	2.2e-10	KMO	8564
ENSG00000096996	279.73	-3.41	0.48	-7.03	2.0e-12	2.3e-10	IL12RB1	3594
ENSG00000196684	1138.53	-3.14	0.45	-7.02	2.2e-12	2.5e-10	HSH2D	84941
ENSG00000042980	1027.85	-3.33	0.47	-7.02	2.3e-12	2.6e-10	ADAM28	10863
ENSG00000230006	895.13	-4.38	0.62	-7.01	2.4e-12	2.6e-10	ANKRD36BP2	645784
ENSG00000106785	1091.58	-2.04	0.29	-7.00	2.5e-12	2.8e-10	TRIM14	9830
ENSG00000269220	126.20	-2.87	0.41	-6.99	2.7e-12	3.0e-10	LINC00528	200298
ENSG00000115232	745.68	-2.68	0.38	-6.98	2.9e-12	3.2e-10	ITGA4	3676
ENSG00000254838	1388.82	-2.89	0.41	-6.97	3.1e-12	3.4e-10	GVINP1	387751
ENSG00000116824	727.42	-3.13	0.45	-6.96	3.3e-12	3.6e-10	CD2	914
ENSG00000188282	89.78	-4.19	0.60	-6.95	3.7e-12	4.0e-10	RUFY4	285180
ENSG00000081237	4243.29	-3.12	0.45	-6.94	3.9e-12	4.2e-10	PTPRC	5788
ENSG00000124203	510.86	-3.29	0.47	-6.94	3.9e-12	4.2e-10	ZNF831	128611
ENSG00000156886	47.34	-4.91	0.71	-6.93	4.3e-12	4.5e-10	ITGAD	3681
ENSG00000110448	468.78	-3.41	0.49	-6.91	4.7e-12	5.0e-10	CD5	921
ENSG00000186517	1767.29	-2.85	0.41	-6.91	5.0e-12	5.2e-10	ARHGAP30	257106
ENSG00000198821	719.73	-2.96	0.43	-6.89	5.5e-12	5.7e-10	CD247	919
ENSG00000243811	486.16	-2.36	0.34	-6.85	7.2e-12	7.4e-10	APOBEC3D	140564
ENSG00000229474	332.35	-2.86	0.42	-6.85	7.4e-12	7.5e-10	PATL2	197135
ENSG00000127152	675.15	-2.20	0.32	-6.85	7.5e-12	7.6e-10	BCL11B	64919
ENSG00000154451	885.15	-3.30	0.48	-6.84	7.9e-12	8.0e-10	GBP5	115362
ENSG00000145649	265.76	-3.38	0.50	-6.82	8.9e-12	8.9e-10	GZMA	3001
ENSG00000167984	1240.40	-2.39	0.35	-6.80	1.0e-11	1.0e-09	NLRC3	197358
ENSG00000214900	151.13	-2.64	0.39	-6.80	1.0e-11	1.0e-09	LINC01588	283551
ENSG00000065357	3663.02	-2.46	0.36	-6.79	1.1e-11	1.1e-09	DGKA	1606
ENSG00000102962	87.49	-4.27	0.63	-6.79	1.1e-11	1.1e-09	CCL22	6367
ENSG00000168918	3150.63	-2.35	0.35	-6.77	1.3e-11	1.3e-09	INPP5D	3635
ENSG00000126860	388.69	-2.87	0.42	-6.77	1.3e-11	1.3e-09	EVI2A	2123
ENSG00000182010	303.05	-3.14	0.46	-6.76	1.4e-11	1.3e-09	RTKN2	219790
ENSG00000228427	26.74	-3.57	0.53	-6.76	1.4e-11	1.3e-09	LOC107985688	107985688
ENSG00000139626	1152.02	-2.26	0.33	-6.76	1.4e-11	1.3e-09	ITGB7	3695
ENSG00000015133	2228.14	-2.40	0.36	-6.75	1.5e-11	1.4e-09	CCDC88C	440193
ENSG00000134516	1685.07	-2.85	0.42	-6.75	1.5e-11	1.4e-09	DOCK2	1794
ENSG00000146094	1017.42	-2.61	0.39	-6.74	1.5e-11	1.5e-09	DOK3	79930
ENSG00000197471	561.09	-2.77	0.41	-6.74	1.6e-11	1.5e-09	SPN	6693
ENSG00000082074	535.10	-2.90	0.43	-6.74	1.6e-11	1.5e-09	FYB1	2533
ENSG00000237914	18.28	-4.87	0.72	-6.73	1.7e-11	1.5e-09	SIRPG-AS1	101929010
ENSG00000110324	2062.37	-2.41	0.36	-6.71	2.0e-11	1.8e-09	IL10RA	3587
ENSG00000127084	1813.78	-2.08	0.31	-6.69	2.2e-11	2.0e-09	FGD3	89846
ENSG00000178999	92.96	-3.55	0.53	-6.68	2.4e-11	2.2e-09	AURKB	9212
ENSG00000145287	218.06	-2.88	0.43	-6.68	2.4e-11	2.2e-09	PLAC8	51316
ENSG00000157303	360.65	-2.02	0.30	-6.68	2.4e-11	2.2e-09	SUSD3	203328
ENSG00000126882	674.55	-2.40	0.36	-6.67	2.6e-11	2.3e-09	FAM78A	286336
ENSG00000100351	318.80	-2.64	0.40	-6.67	2.6e-11	2.3e-09	GRAP2	9402
ENSG00000125245	108.95	-3.77	0.57	-6.66	2.7e-11	2.4e-09	GPR18	2841
ENSG00000137571	57.48	-3.57	0.54	-6.66	2.8e-11	2.5e-09	SLCO5A1	81796
ENSG00000143167	36.86	-4.33	0.65	-6.65	2.9e-11	2.6e-09	GPA33	10223
ENSG00000086730	792.00	-2.57	0.39	-6.65	3.0e-11	2.6e-09	LAT2	7462
ENSG00000020633	828.13	-2.99	0.45	-6.64	3.0e-11	2.7e-09	RUNX3	864
ENSG00000135960	17.02	-5.25	0.79	-6.63	3.4e-11	3.0e-09	EDAR	10913
ENSG00000180448	5433.87	-2.48	0.37	-6.62	3.5e-11	3.0e-09	ARHGAP45	23526
ENSG00000240505	194.19	-7.15	1.08	-6.61	3.8e-11	3.2e-09	TNFRSF13B	23495
ENSG00000164362	16.92	-5.78	0.87	-6.61	3.9e-11	3.3e-09	TERT	7015
ENSG00000178562	397.88	-3.93	0.60	-6.60	4.1e-11	3.5e-09	CD28	940
ENSG00000171848	191.86	-3.55	0.54	-6.60	4.2e-11	3.6e-09	RRM2	6241
ENSG00000134242	351.65	-2.78	0.42	-6.59	4.4e-11	3.7e-09	PTPN22	26191
ENSG00000135426	393.48	-3.10	0.47	-6.58	4.6e-11	3.8e-09	TESPA1	9840
ENSG00000102575	586.33	-2.38	0.36	-6.58	4.6e-11	3.9e-09	ACP5	54
ENSG00000140368	832.77	-2.79	0.42	-6.57	4.9e-11	4.1e-09	PSTPIP1	9051
ENSG00000184922	2543.64	-2.33	0.35	-6.56	5.2e-11	4.3e-09	FMNL1	752
ENSG00000134443	23.56	18.65	2.85	6.56	5.5e-11	4.5e-09	GRP	2922
ENSG00000163600	196.23	-3.96	0.60	-6.55	5.6e-11	4.6e-09	ICOS	29851
ENSG00000186854	220.97	-2.71	0.41	-6.54	6.1e-11	5.0e-09	TRABD2A	129293
ENSG00000116748	50.56	-3.58	0.55	-6.53	6.5e-11	5.3e-09	AMPD1	270
ENSG00000117560	65.53	-2.73	0.42	-6.51	7.3e-11	5.9e-09	FASLG	356
ENSG00000169679	127.09	-3.05	0.47	-6.51	7.3e-11	5.9e-09	BUB1	699
ENSG00000242258	54.79	-4.57	0.70	-6.51	7.7e-11	6.2e-09	LINC00996	285972
ENSG00000256574	14.46	-6.51	1.00	-6.50	7.8e-11	6.3e-09	OR13A1	79290
ENSG00000074966	380.15	-2.87	0.44	-6.50	8.0e-11	6.4e-09	TXK	7294
ENSG00000077984	420.51	-2.75	0.42	-6.48	9.3e-11	7.4e-09	CST7	8530
ENSG00000140451	166.49	-2.30	0.36	-6.47	9.7e-11	7.7e-09	PIF1	80119
ENSG00000204282	959.51	-2.45	0.38	-6.47	1.0e-10	7.9e-09	TNRC6C-AS1	100131096
ENSG00000213809	904.34	-2.82	0.44	-6.46	1.1e-10	8.3e-09	KLRK1	22914
ENSG00000160683	17.08	-5.61	0.87	-6.44	1.2e-10	9.6e-09	CXCR5	643
ENSG00000117215	163.73	-7.09	1.11	-6.42	1.4e-10	1.1e-08	PLA2G2D	26279
ENSG00000127074	130.32	-5.36	0.83	-6.42	1.4e-10	1.1e-08	RGS13	6003
ENSG00000117090	335.39	-3.33	0.52	-6.41	1.4e-10	1.1e-08	SLAMF1	6504
ENSG00000126353	492.55	-2.60	0.41	-6.41	1.5e-10	1.1e-08	CCR7	1236
ENSG00000066279	114.04	-3.10	0.48	-6.40	1.5e-10	1.2e-08	ASPM	259266
ENSG00000064201	185.99	-2.96	0.46	-6.40	1.5e-10	1.2e-08	TSPAN32	10077
ENSG00000188011	83.08	-3.47	0.54	-6.39	1.6e-10	1.2e-08	RTP5	285093
ENSG00000166707	140.92	-2.25	0.35	-6.39	1.6e-10	1.2e-08	ZCCHC18	644353
ENSG00000112195	61.98	-4.23	0.66	-6.39	1.6e-10	1.2e-08	TREML2	79865
ENSG00000181617	403.51	-8.85	1.39	-6.38	1.7e-10	1.3e-08	FDCSP	260436
ENSG00000141524	3991.16	-2.14	0.34	-6.38	1.8e-10	1.3e-08	TMC6	11322
ENSG00000049249	22.64	-4.07	0.64	-6.38	1.8e-10	1.4e-08	TNFRSF9	3604
ENSG00000179715	663.98	-2.37	0.37	-6.36	2.0e-10	1.5e-08	PCED1B	91523
ENSG00000172116	199.75	-2.75	0.43	-6.36	2.1e-10	1.5e-08	CD8B	926
ENSG00000137841	2627.68	-2.55	0.40	-6.34	2.3e-10	1.7e-08	PLCB2	5330
ENSG00000100365	986.25	-2.17	0.34	-6.34	2.3e-10	1.7e-08	NCF4	4689
ENSG00000103522	159.70	-3.29	0.52	-6.34	2.4e-10	1.7e-08	IL21R	50615
ENSG00000162897	78.95	-8.64	1.36	-6.33	2.4e-10	1.7e-08	FCAMR	83953
ENSG00000125910	380.75	-2.24	0.35	-6.33	2.4e-10	1.8e-08	S1PR4	8698
ENSG00000141506	998.02	-2.72	0.43	-6.33	2.4e-10	1.8e-08	PIK3R5	23533
ENSG00000144354	215.97	-2.79	0.44	-6.32	2.7e-10	2.0e-08	CDCA7	83879
ENSG00000188822	193.34	-3.30	0.52	-6.31	2.8e-10	2.1e-08	CNR2	1269
ENSG00000197549	30.14	-8.87	1.41	-6.30	2.9e-10	2.1e-08	PRAMENP	649179
ENSG00000164691	537.55	-2.90	0.46	-6.29	3.3e-10	2.3e-08	TAGAP	117289
ENSG00000162676	259.29	-2.42	0.39	-6.28	3.4e-10	2.4e-08	GFI1	2672
ENSG00000205045	197.51	-2.34	0.37	-6.28	3.4e-10	2.5e-08	SLFN12L	100506736
ENSG00000197520	58.61	-3.96	0.63	-6.27	3.5e-10	2.5e-08	FAM177B	400823
ENSG00000167664	28.86	-3.05	0.49	-6.27	3.6e-10	2.5e-08	TMIGD2	126259
ENSG00000122223	95.94	-2.89	0.46	-6.24	4.4e-10	3.1e-08	CD244	51744
ENSG00000128815	1099.25	-3.31	0.53	-6.23	4.6e-10	3.2e-08	WDFY4	57705
ENSG00000137101	691.00	-2.37	0.38	-6.23	4.6e-10	3.2e-08	CD72	971
ENSG00000204165	47.67	-3.65	0.59	-6.22	4.8e-10	3.4e-08	CXorf65	158830
ENSG00000136167	3536.69	-2.57	0.41	-6.22	4.9e-10	3.4e-08	LCP1	3936
ENSG00000246528	10.50	-5.95	0.96	-6.21	5.2e-10	3.6e-08	LOC101929759	101929759
ENSG00000237499	284.96	-2.63	0.42	-6.21	5.3e-10	3.7e-08	WAKMAR2	100130476
ENSG00000232788	28.13	-2.34	0.38	-6.21	5.4e-10	3.7e-08	ITGA6-AS1	101929947
ENSG00000163519	130.38	-3.50	0.56	-6.21	5.5e-10	3.7e-08	TRAT1	50852
ENSG00000267121	813.19	-2.95	0.48	-6.20	5.6e-10	3.8e-08	LOC339192	339192
ENSG00000165066	16.04	-4.58	0.74	-6.18	6.4e-10	4.3e-08	NKX6-3	157848
ENSG00000180096	34.62	-2.22	0.36	-6.18	6.6e-10	4.4e-08	SEPTIN1	1731
ENSG00000069493	1234.84	-2.42	0.39	-6.17	6.7e-10	4.5e-08	CLEC2D	29121
ENSG00000073861	176.67	-2.63	0.43	-6.17	6.8e-10	4.5e-08	TBX21	30009
ENSG00000171241	105.73	-2.94	0.48	-6.17	7.0e-10	4.7e-08	SHCBP1	79801
ENSG00000136541	117.63	-3.36	0.55	-6.16	7.1e-10	4.7e-08	ERMN	57471
ENSG00000123219	88.45	-2.15	0.35	-6.15	7.6e-10	5.0e-08	CENPK	64105
ENSG00000130812	56.45	-2.99	0.49	-6.15	7.6e-10	5.0e-08	ANGPTL6	83854
ENSG00000164483	214.56	-2.94	0.48	-6.15	7.7e-10	5.0e-08	SAMD3	154075
ENSG00000049768	114.45	-2.57	0.42	-6.14	8.3e-10	5.4e-08	FOXP3	50943
ENSG00000186185	103.07	-3.15	0.51	-6.13	8.5e-10	5.6e-08	KIF18B	146909
ENSG00000114200	124.34	2.11	0.34	6.13	8.9e-10	5.7e-08	BCHE	590
ENSG00000153563	865.55	-2.24	0.37	-6.12	9.6e-10	6.2e-08	CD8A	925
ENSG00000118308	1124.40	-2.32	0.38	-6.11	9.8e-10	6.3e-08	LRMP	4033
ENSG00000198846	346.86	-2.00	0.33	-6.10	1.1e-09	6.9e-08	TOX	9760
ENSG00000134539	112.52	-2.08	0.34	-6.10	1.1e-09	7.0e-08	KLRD1	3824
ENSG00000077420	829.05	-2.03	0.33	-6.09	1.2e-09	7.3e-08	APBB1IP	54518
ENSG00000141293	239.61	-2.44	0.40	-6.07	1.3e-09	7.9e-08	SKAP1	8631
ENSG00000070915	19.21	-3.38	0.56	-6.07	1.3e-09	8.3e-08	SLC12A3	6559
ENSG00000138755	1841.40	-3.67	0.61	-6.06	1.4e-09	8.8e-08	CXCL9	4283
ENSG00000089820	4408.06	-2.22	0.37	-6.04	1.6e-09	9.7e-08	ARHGAP4	393
ENSG00000171320	23.91	-2.98	0.49	-6.03	1.6e-09	1.0e-07	ESCO2	157570
ENSG00000141968	727.95	-2.62	0.43	-6.03	1.6e-09	1.0e-07	VAV1	7409
ENSG00000104972	637.43	-3.19	0.53	-6.02	1.7e-09	1.1e-07	LILRB1	10859
ENSG00000182183	111.20	-2.51	0.42	-6.01	1.8e-09	1.1e-07	SHISAL2A	348378
ENSG00000156970	124.85	-2.54	0.42	-6.01	1.9e-09	1.2e-07	BUB1B	701
ENSG00000246582	56.58	-2.20	0.37	-6.01	1.9e-09	1.2e-07	LOC389641	389641
ENSG00000161405	184.89	-3.57	0.60	-6.00	2.0e-09	1.2e-07	IKZF3	22806
ENSG00000142347	1649.55	-2.08	0.35	-5.99	2.1e-09	1.2e-07	MYO1F	4542
ENSG00000101194	1761.68	-2.76	0.46	-5.99	2.1e-09	1.3e-07	SLC17A9	63910
ENSG00000251002	13.47	-4.61	0.77	-5.98	2.2e-09	1.3e-07	LOC105370401	105370401
ENSG00000234572	10.73	-6.66	1.11	-5.98	2.3e-09	1.4e-07	LINC01800	101927438
ENSG00000175063	112.10	-3.07	0.51	-5.98	2.3e-09	1.4e-07	UBE2C	11065
ENSG00000213886	44.34	-5.57	0.93	-5.96	2.5e-09	1.5e-07	UBD	10537
ENSG00000165304	52.35	-2.96	0.50	-5.96	2.5e-09	1.5e-07	MELK	9833
ENSG00000073737	48.66	-2.77	0.46	-5.96	2.6e-09	1.5e-07	DHRS9	10170
ENSG00000134028	162.53	-4.53	0.76	-5.95	2.6e-09	1.5e-07	ADAMDEC1	27299
ENSG00000181036	125.93	-2.90	0.49	-5.95	2.7e-09	1.6e-07	FCRL6	343413
ENSG00000172575	419.38	-2.68	0.45	-5.94	2.8e-09	1.6e-07	RASGRP1	10125
ENSG00000023892	2014.24	-2.07	0.35	-5.93	3.0e-09	1.7e-07	DEF6	50619
ENSG00000153898	283.70	-3.35	0.57	-5.92	3.1e-09	1.8e-07	MCOLN2	255231
ENSG00000137804	236.16	-2.32	0.39	-5.92	3.1e-09	1.8e-07	NUSAP1	51203
ENSG00000113263	1144.03	-3.22	0.54	-5.92	3.2e-09	1.8e-07	ITK	3702
ENSG00000237945	471.01	-2.07	0.35	-5.91	3.4e-09	2.0e-07	LINC00649	100506334
ENSG00000148773	478.57	-3.01	0.51	-5.90	3.5e-09	2.0e-07	MKI67	4288
ENSG00000140030	129.41	-2.45	0.42	-5.89	3.9e-09	2.2e-07	GPR65	8477
ENSG00000143185	35.99	-3.38	0.57	-5.88	4.1e-09	2.4e-07	XCL2	6846
ENSG00000023445	2229.36	-2.52	0.43	-5.87	4.2e-09	2.4e-07	BIRC3	330
ENSG00000112799	152.99	-2.73	0.47	-5.86	4.7e-09	2.7e-07	LY86	9450
ENSG00000074370	5639.37	-2.08	0.36	-5.85	4.9e-09	2.8e-07	ATP2A3	489
ENSG00000089692	272.00	-2.69	0.46	-5.85	5.0e-09	2.8e-07	LAG3	3902
ENSG00000188263	29.39	-4.31	0.74	-5.84	5.2e-09	2.9e-07	IL17REL	400935
ENSG00000167476	115.03	-3.56	0.61	-5.83	5.5e-09	3.0e-07	JSRP1	126306
ENSG00000088340	1127.95	-3.14	0.54	-5.82	5.9e-09	3.3e-07	FER1L4	80307
ENSG00000204252	1384.61	-2.11	0.36	-5.80	6.4e-09	3.5e-07	HLA-DOA	3111
ENSG00000160593	792.04	-2.25	0.39	-5.80	6.6e-09	3.6e-07	JAML	120425
ENSG00000123485	87.96	-3.00	0.52	-5.79	7.0e-09	3.8e-07	HJURP	55355
ENSG00000135898	40.16	-3.19	0.55	-5.79	7.2e-09	3.9e-07	GPR55	9290
ENSG00000115165	1011.84	-2.77	0.48	-5.78	7.4e-09	4.0e-07	CYTIP	9595
ENSG00000075218	77.28	-2.32	0.40	-5.77	7.9e-09	4.3e-07	GTSE1	51512
ENSG00000100162	71.73	-2.87	0.50	-5.77	8.0e-09	4.4e-07	CENPM	79019
ENSG00000007264	256.05	-2.12	0.37	-5.76	8.2e-09	4.4e-07	MATK	4145
ENSG00000120280	79.82	-2.64	0.46	-5.76	8.4e-09	4.5e-07	CXorf21	80231
ENSG00000140678	1886.44	-2.69	0.47	-5.74	9.2e-09	4.9e-07	ITGAX	3687
ENSG00000183542	93.06	-2.31	0.40	-5.74	9.2e-09	4.9e-07	KLRC4	8302
ENSG00000235621	73.66	-5.38	0.94	-5.74	9.7e-09	5.2e-07	LINC00494	284749
ENSG00000205784	41.46	-3.21	0.56	-5.74	9.7e-09	5.2e-07	ARRDC5	645432
ENSG00000245648	48.61	-2.54	0.44	-5.73	1.0e-08	5.3e-07	LOC101928100	101928100
ENSG00000089685	44.79	-2.80	0.49	-5.73	1.0e-08	5.3e-07	BIRC5	332
ENSG00000121966	6073.41	-2.95	0.52	-5.73	1.0e-08	5.4e-07	CXCR4	7852
ENSG00000051341	75.63	-2.93	0.51	-5.72	1.0e-08	5.5e-07	POLQ	10721
ENSG00000233360	7.79	-2.98	0.52	-5.72	1.1e-08	5.6e-07	LOC101927051	101927051
ENSG00000245954	30.44	-4.55	0.79	-5.72	1.1e-08	5.7e-07	LINC02273	100996286
ENSG00000177699	6.07	-4.28	0.75	-5.71	1.1e-08	5.8e-07	LOC100129540	100129540
ENSG00000101082	176.51	-2.63	0.46	-5.71	1.1e-08	5.9e-07	SLA2	84174
ENSG00000109805	81.66	-2.60	0.46	-5.70	1.2e-08	6.3e-07	NCAPG	64151
ENSG00000118513	99.57	-3.17	0.56	-5.69	1.2e-08	6.5e-07	MYB	4602
ENSG00000131401	548.49	-3.11	0.55	-5.69	1.3e-08	6.6e-07	NAPSB	256236
ENSG00000163376	179.17	-2.43	0.43	-5.69	1.3e-08	6.7e-07	KBTBD8	84541
ENSG00000146670	143.35	-2.02	0.36	-5.68	1.4e-08	7.1e-07	CDCA5	113130
ENSG00000135476	124.18	-2.42	0.43	-5.67	1.4e-08	7.2e-07	ESPL1	9700
ENSG00000253490	17.07	-4.63	0.82	-5.67	1.4e-08	7.2e-07	LINC02099	101929450
ENSG00000203710	204.31	-2.79	0.49	-5.65	1.6e-08	8.2e-07	CR1	1378
ENSG00000049247	16.49	-5.04	0.89	-5.64	1.7e-08	8.5e-07	UTS2	10911
ENSG00000172543	365.24	-2.55	0.45	-5.64	1.7e-08	8.5e-07	CTSW	1521
ENSG00000236320	24.36	-3.13	0.56	-5.64	1.7e-08	8.8e-07	SLFN14	342618
ENSG00000099958	2327.84	-2.26	0.40	-5.63	1.8e-08	9.1e-07	DERL3	91319
ENSG00000140968	1478.13	-2.62	0.47	-5.62	1.9e-08	9.8e-07	IRF8	3394
ENSG00000121152	76.69	-2.36	0.42	-5.60	2.2e-08	1.1e-06	NCAPH	23397
ENSG00000111863	70.47	-2.40	0.43	-5.58	2.5e-08	1.2e-06	ADTRP	84830
ENSG00000156127	169.87	-2.45	0.44	-5.57	2.6e-08	1.3e-06	BATF	10538
ENSG00000100055	1351.72	-2.22	0.40	-5.56	2.7e-08	1.3e-06	CYTH4	27128
ENSG00000232810	92.96	-4.01	0.72	-5.55	2.9e-08	1.4e-06	TNF	7124
ENSG00000183813	147.90	-3.64	0.66	-5.54	3.0e-08	1.4e-06	CCR4	1233
ENSG00000160224	54.03	-3.37	0.61	-5.54	3.0e-08	1.5e-06	AIRE	326
ENSG00000154839	26.76	-2.56	0.46	-5.54	3.0e-08	1.5e-06	SKA1	220134
ENSG00000174255	90.92	-3.50	0.63	-5.54	3.0e-08	1.5e-06	ZNF80	7634
ENSG00000173762	528.24	-2.47	0.45	-5.53	3.1e-08	1.5e-06	CD7	924
ENSG00000105967	382.39	-2.22	0.40	-5.53	3.2e-08	1.6e-06	TFEC	22797
ENSG00000152270	373.70	-2.57	0.46	-5.52	3.4e-08	1.6e-06	PDE3B	5140
ENSG00000197540	144.50	-2.58	0.47	-5.52	3.4e-08	1.6e-06	GZMM	3004
ENSG00000012779	1314.57	-2.32	0.42	-5.52	3.5e-08	1.7e-06	ALOX5	240
ENSG00000180535	31.95	-2.96	0.54	-5.50	3.8e-08	1.8e-06	BHLHA15	168620
ENSG00000163564	462.98	-3.16	0.58	-5.50	3.9e-08	1.8e-06	PYHIN1	149628
ENSG00000254887	12.31	-4.04	0.73	-5.50	3.9e-08	1.8e-06	LOC100505622	100505622
ENSG00000152207	56.44	-2.42	0.44	-5.48	4.2e-08	2.0e-06	CYSLTR2	57105
ENSG00000186810	186.95	-2.71	0.49	-5.48	4.3e-08	2.0e-06	CXCR3	2833
ENSG00000174946	225.35	-3.15	0.57	-5.48	4.3e-08	2.0e-06	GPR171	29909
ENSG00000108405	264.87	-2.46	0.45	-5.48	4.3e-08	2.0e-06	P2RX1	5023
ENSG00000179253	4.38	-5.14	0.94	-5.47	4.4e-08	2.1e-06	LOC100128310	100128310
ENSG00000123338	1092.73	-2.30	0.42	-5.47	4.4e-08	2.1e-06	NCKAP1L	3071
ENSG00000139618	105.79	-2.05	0.38	-5.45	5.1e-08	2.4e-06	BRCA2	675
ENSG00000109684	106.06	-3.63	0.67	-5.44	5.2e-08	2.4e-06	CLNK	116449
ENSG00000167094	141.40	-2.20	0.40	-5.44	5.2e-08	2.4e-06	TTC16	158248
ENSG00000211689	84.74	-2.84	0.52	-5.44	5.3e-08	2.5e-06	TARP	445347
ENSG00000221946	32.26	-2.66	0.49	-5.44	5.5e-08	2.5e-06	FXYD7	53822
ENSG00000231964	36.37	-2.94	0.54	-5.43	5.6e-08	2.6e-06	LOC102724323	102724323
ENSG00000159556	10.15	-4.55	0.84	-5.43	5.7e-08	2.6e-06	ISL2	64843
ENSG00000253522	119.42	-2.90	0.53	-5.43	5.7e-08	2.6e-06	MIR3142HG	107075116
ENSG00000135925	96.55	-3.16	0.58	-5.43	5.8e-08	2.6e-06	WNT10A	80326
ENSG00000120949	46.74	-2.30	0.42	-5.42	5.8e-08	2.7e-06	TNFRSF8	943
ENSG00000224557	20.27	-3.12	0.58	-5.42	5.9e-08	2.7e-06	HLA-DPB2	3116
ENSG00000132744	36.52	-3.97	0.73	-5.41	6.2e-08	2.8e-06	ACY3	91703
ENSG00000153789	9.78	-4.33	0.80	-5.41	6.3e-08	2.9e-06	FAM92B	339145
ENSG00000105501	58.61	-2.22	0.41	-5.40	6.6e-08	3.0e-06	SIGLEC5	8778
ENSG00000127561	73.49	-2.25	0.42	-5.39	7.2e-08	3.2e-06	SYNGR3	9143
ENSG00000105374	398.26	-2.66	0.49	-5.38	7.5e-08	3.4e-06	NKG7	4818
ENSG00000169495	33.19	-2.13	0.40	-5.37	7.7e-08	3.5e-06	HTRA4	203100
ENSG00000188042	1333.74	-2.01	0.38	-5.36	8.2e-08	3.6e-06	ARL4C	10123
ENSG00000140379	152.40	-2.57	0.48	-5.35	9.0e-08	4.0e-06	BCL2A1	597
ENSG00000061656	239.64	-2.11	0.40	-5.34	9.2e-08	4.0e-06	SPAG4	6676
ENSG00000111732	35.65	-5.37	1.01	-5.34	9.4e-08	4.1e-06	AICDA	57379
ENSG00000183150	19.99	-2.44	0.46	-5.33	9.7e-08	4.2e-06	GPR19	2842
ENSG00000102445	161.86	-2.24	0.42	-5.33	9.9e-08	4.3e-06	RUBCNL	80183
ENSG00000136286	1442.80	-2.61	0.49	-5.32	1.0e-07	4.5e-06	MYO1G	64005
ENSG00000126787	62.17	-3.43	0.64	-5.32	1.1e-07	4.6e-06	DLGAP5	9787
ENSG00000268758	74.59	-2.79	0.53	-5.30	1.1e-07	4.9e-06	ADGRE4P	326342
ENSG00000152213	88.50	-2.05	0.39	-5.29	1.2e-07	5.1e-06	ARL11	115761
ENSG00000172673	171.59	-2.58	0.49	-5.29	1.2e-07	5.3e-06	THEMIS	387357
ENSG00000163630	63.59	-3.35	0.63	-5.28	1.3e-07	5.5e-06	SYNPR	132204
ENSG00000011590	135.48	-2.63	0.50	-5.27	1.3e-07	5.6e-06	ZBTB32	27033
ENSG00000229228	10.05	-3.55	0.67	-5.27	1.4e-07	5.8e-06	LINC00582	100287814
ENSG00000253686	25.08	-3.11	0.59	-5.27	1.4e-07	5.8e-06	LINC01484	101928136
ENSG00000226025	56.41	-3.82	0.73	-5.26	1.4e-07	6.1e-06	LGALS17A	400696
ENSG00000142583	245.92	-2.64	0.50	-5.26	1.5e-07	6.1e-06	SLC2A5	6518
ENSG00000124557	16.19	-3.00	0.57	-5.26	1.5e-07	6.2e-06	BTN1A1	696
ENSG00000120659	43.46	-5.10	0.97	-5.25	1.5e-07	6.3e-06	TNFSF11	8600
ENSG00000060140	32.48	-2.49	0.47	-5.25	1.5e-07	6.4e-06	STYK1	55359
ENSG00000138623	426.67	-2.17	0.41	-5.25	1.5e-07	6.5e-06	SEMA7A	8482
ENSG00000105011	107.44	-2.20	0.42	-5.24	1.6e-07	6.7e-06	ASF1B	55723
ENSG00000026559	39.57	-2.47	0.47	-5.22	1.8e-07	7.2e-06	KCNG1	3755
ENSG00000110876	665.35	-2.10	0.40	-5.21	1.8e-07	7.6e-06	SELPLG	6404
ENSG00000205436	152.67	-2.95	0.56	-5.21	1.9e-07	7.6e-06	EXOC3L4	91828
ENSG00000218018	17.34	-2.29	0.44	-5.20	2.0e-07	8.3e-06	LOC100291105	100291105
ENSG00000158485	9.84	-4.25	0.82	-5.19	2.1e-07	8.5e-06	CD1B	910
ENSG00000151790	33.12	-3.63	0.70	-5.18	2.2e-07	9.1e-06	TDO2	6999
ENSG00000250155	11.68	-3.10	0.60	-5.18	2.2e-07	9.1e-06	LOC107986412	107986412
ENSG00000180549	69.07	-2.54	0.49	-5.17	2.4e-07	9.7e-06	FUT7	2529
ENSG00000115956	1084.22	-2.20	0.43	-5.17	2.4e-07	9.7e-06	PLEK	5341
ENSG00000118193	44.21	-2.21	0.43	-5.15	2.6e-07	1.0e-05	KIF14	9928
ENSG00000197299	143.60	-2.04	0.40	-5.15	2.7e-07	1.1e-05	BLM	641
ENSG00000174371	36.95	-2.04	0.40	-5.13	2.9e-07	1.2e-05	EXO1	9156
ENSG00000106952	151.55	-2.80	0.55	-5.11	3.2e-07	1.3e-05	TNFSF8	944
ENSG00000245466	17.39	-3.46	0.68	-5.10	3.4e-07	1.3e-05	LOC101928075	101928075
ENSG00000117724	179.32	-2.09	0.41	-5.10	3.5e-07	1.3e-05	CENPF	1063
ENSG00000160791	277.00	-2.13	0.42	-5.07	4.0e-07	1.6e-05	CCR5	1234
ENSG00000216863	9.33	-4.38	0.87	-5.04	4.7e-07	1.8e-05	LY86-AS1	285780
ENSG00000185527	32.65	-2.25	0.45	-5.03	5.0e-07	1.9e-05	PDE6G	5148
ENSG00000251301	60.41	-3.07	0.61	-5.02	5.2e-07	2.0e-05	LINC02384	100507195
ENSG00000189057	49.35	-2.42	0.48	-5.01	5.5e-07	2.1e-05	FAM111B	374393
ENSG00000230937	81.15	-3.59	0.72	-5.00	5.8e-07	2.2e-05	MIR205HG	642587
ENSG00000007968	145.96	-2.63	0.53	-5.00	5.9e-07	2.2e-05	E2F2	1870
ENSG00000093009	54.14	-2.22	0.44	-4.99	6.1e-07	2.3e-05	CDC45	8318
ENSG00000111537	30.77	-3.82	0.77	-4.95	7.4e-07	2.7e-05	IFNG	3458
ENSG00000105255	36.63	-2.41	0.49	-4.94	7.9e-07	2.9e-05	FSD1	79187
ENSG00000121807	336.84	-2.51	0.51	-4.94	7.9e-07	2.9e-05	CCR2	729230
ENSG00000143228	67.52	-2.11	0.43	-4.92	8.7e-07	3.2e-05	NUF2	83540
ENSG00000012124	2713.50	-3.07	0.63	-4.90	9.6e-07	3.5e-05	CD22	933
ENSG00000248329	4.89	-5.63	1.15	-4.90	9.8e-07	3.5e-05	APELA	100506013
ENSG00000168685	3193.54	-2.95	0.60	-4.89	9.9e-07	3.5e-05	IL7R	3575
ENSG00000179813	11.06	-4.76	0.97	-4.89	9.9e-07	3.5e-05	FAM216B	144809
ENSG00000143869	43.23	-2.44	0.50	-4.89	1.0e-06	3.6e-05	GDF7	151449
ENSG00000265148	43.22	-2.03	0.42	-4.87	1.1e-06	4.0e-05	TSPOAP1-AS1	100506779
ENSG00000120332	270.61	2.57	0.53	4.85	1.2e-06	4.3e-05	TNN	63923
ENSG00000189238	34.07	-2.45	0.50	-4.85	1.2e-06	4.3e-05	LINC00943	100507206
ENSG00000223823	10.34	-2.52	0.52	-4.85	1.2e-06	4.3e-05	LINC01342	254099
ENSG00000131747	311.35	-2.23	0.46	-4.85	1.3e-06	4.4e-05	TOP2A	7153
ENSG00000260101	25.35	-2.34	0.48	-4.84	1.3e-06	4.6e-05	LOC101927402	101927402
ENSG00000234965	7.21	-5.43	1.12	-4.83	1.3e-06	4.7e-05	SHISA8	440829
ENSG00000165480	25.08	-2.45	0.51	-4.83	1.4e-06	4.8e-05	SKA3	221150
ENSG00000230709	9.90	-4.02	0.83	-4.83	1.4e-06	4.8e-05	LOC284191	284191
ENSG00000109101	65.96	-2.11	0.44	-4.82	1.4e-06	5.0e-05	FOXN1	8456
ENSG00000189430	12.94	-2.41	0.50	-4.82	1.4e-06	5.0e-05	NCR1	9437
ENSG00000152495	392.69	-2.65	0.55	-4.80	1.6e-06	5.4e-05	CAMK4	814
ENSG00000214894	23.76	-3.11	0.65	-4.79	1.6e-06	5.6e-05	LINC00243	401247
ENSG00000158477	22.99	-5.09	1.07	-4.77	1.8e-06	6.2e-05	CD1A	909
ENSG00000136492	40.74	-2.25	0.47	-4.77	1.8e-06	6.2e-05	BRIP1	83990
ENSG00000179583	3030.63	-2.01	0.42	-4.76	1.9e-06	6.5e-05	CIITA	4261
ENSG00000173585	8.82	-2.59	0.55	-4.75	2.0e-06	6.7e-05	CCR9	10803
ENSG00000050730	19.32	-3.12	0.66	-4.74	2.1e-06	7.1e-05	TNIP3	79931
ENSG00000186891	184.16	-2.75	0.58	-4.74	2.1e-06	7.1e-05	TNFRSF18	8784
ENSG00000129204	428.14	2.09	0.44	4.74	2.1e-06	7.1e-05	USP6	9098
ENSG00000177272	229.31	-2.08	0.44	-4.73	2.2e-06	7.4e-05	KCNA3	3738
ENSG00000100985	292.17	-2.80	0.59	-4.71	2.4e-06	8.0e-05	MMP9	4318
ENSG00000166428	129.30	-2.51	0.53	-4.70	2.6e-06	8.5e-05	PLD4	122618
ENSG00000129810	25.65	-2.46	0.52	-4.69	2.7e-06	8.9e-05	SGO1	151648
ENSG00000006128	298.53	3.09	0.66	4.66	3.2e-06	1.0e-04	TAC1	6863
ENSG00000170486	52.53	-3.42	0.74	-4.65	3.4e-06	1.1e-04	KRT72	140807
ENSG00000246084	10.33	-3.56	0.77	-4.64	3.5e-06	1.1e-04	LINC02325	101929241
ENSG00000261448	8.99	-2.89	0.62	-4.64	3.5e-06	1.1e-04	LOC102723692	102723692
ENSG00000239961	14.34	-2.52	0.54	-4.64	3.5e-06	1.1e-04	LILRA4	23547
ENSG00000024526	36.20	-2.30	0.50	-4.63	3.6e-06	1.1e-04	DEPDC1	55635
ENSG00000105366	66.13	-3.06	0.66	-4.62	3.9e-06	1.2e-04	SIGLEC8	27181
ENSG00000255833	22.38	-3.56	0.77	-4.61	4.0e-06	1.3e-04	TIFAB	497189
ENSG00000158488	77.18	-3.71	0.81	-4.59	4.5e-06	1.4e-04	CD1E	913
ENSG00000164512	80.79	-3.79	0.83	-4.58	4.6e-06	1.4e-04	ANKRD55	79722
ENSG00000187808	29.04	-2.47	0.54	-4.58	4.7e-06	1.5e-04	SOWAHD	347454
ENSG00000179873	8.88	-3.97	0.87	-4.57	4.8e-06	1.5e-04	NLRP11	204801
ENSG00000058335	38.67	-2.00	0.44	-4.56	5.1e-06	1.6e-04	RASGRF1	5923
ENSG00000166736	39.63	-4.36	0.96	-4.55	5.3e-06	1.6e-04	HTR3A	3359
ENSG00000187510	24.64	-6.05	1.33	-4.55	5.3e-06	1.6e-04	C12orf74	338809
ENSG00000145850	134.79	-3.00	0.66	-4.55	5.5e-06	1.7e-04	TIMD4	91937
ENSG00000127564	80.30	-2.07	0.46	-4.54	5.7e-06	1.8e-04	PKMYT1	9088
ENSG00000166268	25.32	-2.74	0.60	-4.53	5.8e-06	1.8e-04	MYRFL	196446
ENSG00000263413	2.00	-4.97	1.10	-4.53	5.8e-06	1.8e-04	MIR4538	100616276
ENSG00000185697	348.59	-2.19	0.48	-4.53	5.9e-06	1.8e-04	MYBL1	4603
ENSG00000172724	3885.91	-3.60	0.80	-4.52	6.1e-06	1.8e-04	CCL19	6363
ENSG00000236977	3.04	-3.61	0.80	-4.52	6.2e-06	1.9e-04	ANKRD44-IT1	101927547
ENSG00000090889	59.97	-2.11	0.47	-4.52	6.2e-06	1.9e-04	KIF4A	24137
ENSG00000188886	10.63	-3.67	0.81	-4.52	6.2e-06	1.9e-04	ASTL	431705
ENSG00000105639	3460.33	-2.03	0.45	-4.51	6.3e-06	1.9e-04	JAK3	3718
ENSG00000114013	222.88	-2.00	0.44	-4.51	6.4e-06	1.9e-04	CD86	942
ENSG00000107593	6.77	-3.26	0.72	-4.51	6.6e-06	2.0e-04	PKD2L1	9033
ENSG00000113249	13.23	-3.53	0.79	-4.49	7.0e-06	2.1e-04	HAVCR1	26762
ENSG00000159337	7.06	-3.34	0.75	-4.45	8.5e-06	2.5e-04	PLA2G4D	283748
ENSG00000204277	7.23	-3.32	0.75	-4.41	1.0e-05	3.0e-04	LINC01993	100996291
ENSG00000253364	31.17	-3.05	0.69	-4.41	1.0e-05	3.0e-04	COPDA1	115253418
ENSG00000125084	13.22	-2.19	0.50	-4.40	1.1e-05	3.1e-04	WNT1	7471
ENSG00000233308	2.49	-4.59	1.05	-4.39	1.1e-05	3.2e-04	OSTN-AS1	106480738
ENSG00000148204	84.17	-2.26	0.52	-4.38	1.2e-05	3.4e-04	CRB2	286204
ENSG00000228590	6.43	-4.14	0.95	-4.37	1.2e-05	3.5e-04	MIR4432HG	106660609
ENSG00000148600	177.71	-2.24	0.51	-4.37	1.3e-05	3.5e-04	CDHR1	92211
ENSG00000254211	7.61	-3.15	0.72	-4.35	1.3e-05	3.7e-04	LINC01485	101928154
ENSG00000142512	374.65	-2.53	0.58	-4.34	1.5e-05	4.0e-04	SIGLEC10	89790
ENSG00000124721	47.05	-3.07	0.71	-4.33	1.5e-05	4.0e-04	DNAH8	1769
ENSG00000161270	22.82	-3.82	0.88	-4.33	1.5e-05	4.1e-04	NPHS1	4868
ENSG00000186049	10.72	-2.55	0.59	-4.33	1.5e-05	4.1e-04	KRT73	319101
ENSG00000133105	15.25	3.92	0.91	4.33	1.5e-05	4.1e-04	RXFP2	122042
ENSG00000174885	60.33	-2.53	0.59	-4.31	1.6e-05	4.5e-04	NLRP6	171389
ENSG00000169575	2.94	-5.01	1.16	-4.30	1.7e-05	4.6e-04	VPREB1	7441
ENSG00000155307	398.08	-2.10	0.49	-4.28	1.9e-05	5.0e-04	SAMSN1	64092
ENSG00000162366	102.34	-2.20	0.52	-4.27	1.9e-05	5.2e-04	PDZK1IP1	10158
ENSG00000181143	385.07	-3.51	0.82	-4.26	2.0e-05	5.4e-04	MUC16	94025
ENSG00000214999	15.30	-2.45	0.58	-4.26	2.0e-05	5.4e-04	LOC107985075	107985075
ENSG00000260228	8.66	-2.43	0.57	-4.25	2.1e-05	5.6e-04	LOC102724163	102724163
ENSG00000236081	5.19	-4.31	1.01	-4.25	2.2e-05	5.7e-04	ELFN1-AS1	101927125
ENSG00000232629	334.74	-2.64	0.62	-4.24	2.3e-05	6.0e-04	HLA-DQB2	3120
ENSG00000253633	6.93	-3.85	0.91	-4.23	2.3e-05	6.0e-04	LOC107986898	107986898
ENSG00000122025	84.00	-2.44	0.58	-4.23	2.3e-05	6.1e-04	FLT3	2322
ENSG00000057294	126.29	-2.08	0.49	-4.23	2.3e-05	6.2e-04	PKP2	5318
ENSG00000170858	3.80	-2.75	0.65	-4.22	2.4e-05	6.3e-04	LILRP2	79166
ENSG00000164112	14.24	-2.58	0.61	-4.21	2.6e-05	6.8e-04	TMEM155	132332
ENSG00000105492	17.05	-2.82	0.67	-4.19	2.8e-05	7.2e-04	SIGLEC6	946
ENSG00000164485	3.88	-5.83	1.39	-4.19	2.8e-05	7.3e-04	IL22RA2	116379
ENSG00000167769	12.90	-2.06	0.49	-4.19	2.8e-05	7.3e-04	ACER1	125981
ENSG00000116147	42.65	-2.58	0.62	-4.18	2.9e-05	7.4e-04	TNR	7143
ENSG00000131650	14.01	-2.48	0.59	-4.18	2.9e-05	7.5e-04	KREMEN2	79412
ENSG00000102245	114.28	-2.46	0.59	-4.18	2.9e-05	7.5e-04	CD40LG	959
ENSG00000115163	29.30	-2.17	0.52	-4.17	3.0e-05	7.6e-04	CENPA	1058
ENSG00000266913	2.98	-3.73	0.90	-4.14	3.4e-05	8.6e-04	LINC01841	105372288
ENSG00000213231	4.13	-3.81	0.92	-4.14	3.5e-05	8.8e-04	TCL1B	9623
ENSG00000091181	12.89	-2.50	0.61	-4.12	3.8e-05	9.4e-04	IL5RA	3568
ENSG00000181074	40.60	-2.50	0.61	-4.12	3.8e-05	9.5e-04	OR52N4	390072
ENSG00000144218	372.43	-2.06	0.50	-4.12	3.8e-05	9.5e-04	AFF3	3899
ENSG00000203721	5.53	-2.01	0.49	-4.12	3.8e-05	9.5e-04	LINC00862	554279
ENSG00000110848	1023.97	-2.32	0.56	-4.11	3.9e-05	9.6e-04	CD69	969
ENSG00000073734	8.92	-2.50	0.61	-4.11	4.0e-05	9.9e-04	ABCB11	8647
ENSG00000137673	23.60	-3.21	0.78	-4.11	4.0e-05	9.9e-04	MMP7	4316
ENSG00000158481	146.38	-2.60	0.64	-4.10	4.1e-05	1.0e-03	CD1C	911
ENSG00000144460	7.44	-3.97	0.97	-4.10	4.1e-05	1.0e-03	NYAP2	57624
ENSG00000225362	35.25	2.21	0.54	4.10	4.1e-05	1.0e-03	CT62	196993
ENSG00000167634	6.51	-2.55	0.63	-4.08	4.5e-05	1.1e-03	NLRP7	199713
ENSG00000237484	15.36	-2.06	0.51	-4.07	4.7e-05	1.1e-03	LINC01684	105372751
ENSG00000231621	6.58	-3.55	0.88	-4.05	5.0e-05	1.2e-03	ANKRD44-AS1	101927596
ENSG00000143552	143.99	3.59	0.89	4.02	5.7e-05	1.3e-03	NUP210L	91181
ENSG00000169413	401.36	-2.04	0.51	-4.02	5.7e-05	1.3e-03	RNASE6	6039
ENSG00000187997	6.49	-4.09	1.03	-3.98	6.8e-05	1.6e-03	C17orf99	100141515
ENSG00000090104	4596.00	-2.42	0.61	-3.98	7.0e-05	1.6e-03	RGS1	5996
ENSG00000227145	8.84	-4.17	1.05	-3.97	7.2e-05	1.7e-03	IL21-AS1	100996941
ENSG00000235295	2.39	-4.13	1.04	-3.96	7.6e-05	1.7e-03	LINC01634	100192420
ENSG00000093134	24.68	-2.19	0.55	-3.95	7.9e-05	1.8e-03	VNN3	55350
ENSG00000147614	11.31	-2.55	0.65	-3.94	8.2e-05	1.9e-03	ATP6V0D2	245972
ENSG00000179934	4.16	-3.82	0.97	-3.92	8.7e-05	2.0e-03	CCR8	1237
ENSG00000152192	6.95	-2.69	0.69	-3.92	8.9e-05	2.0e-03	POU4F1	5457
ENSG00000233673	24.19	-2.52	0.65	-3.90	9.6e-05	2.1e-03	ANAPC1P1	100286979
ENSG00000231752	6.93	-2.43	0.62	-3.90	9.6e-05	2.2e-03	EMBP1	647121
ENSG00000231682	2.83	-4.82	1.24	-3.90	9.8e-05	2.2e-03	LINC01891	105373934
ENSG00000238266	2.00	-4.79	1.24	-3.87	1.1e-04	2.4e-03	LINC00707	100507127
ENSG00000215644	24.88	-2.69	0.70	-3.86	1.1e-04	2.5e-03	GCGR	2642
ENSG00000102970	22.77	-3.52	0.91	-3.86	1.2e-04	2.5e-03	CCL17	6361
ENSG00000169245	334.62	-2.86	0.75	-3.83	1.3e-04	2.7e-03	CXCL10	3627
ENSG00000260802	9.70	-3.53	0.92	-3.83	1.3e-04	2.8e-03	SERTM2	401613
ENSG00000179840	4.32	-3.21	0.84	-3.82	1.3e-04	2.9e-03	PIK3CD-AS1	644997
ENSG00000114455	9.48	-2.13	0.56	-3.81	1.4e-04	3.0e-03	HHLA2	11148
ENSG00000263080	5.94	-2.61	0.69	-3.81	1.4e-04	3.0e-03	LOC105371083	105371083
ENSG00000109674	10.31	-2.27	0.60	-3.80	1.5e-04	3.1e-03	NEIL3	55247
ENSG00000146049	11.35	2.42	0.64	3.79	1.5e-04	3.2e-03	KAAG1	353219
ENSG00000150556	18.44	-2.40	0.63	-3.79	1.5e-04	3.2e-03	LYPD6B	130576
ENSG00000166603	2.76	-5.30	1.40	-3.79	1.5e-04	3.2e-03	MC4R	4160
ENSG00000160505	15.67	-3.76	1.00	-3.78	1.6e-04	3.4e-03	NLRP4	147945
ENSG00000166211	3.85	-4.64	1.23	-3.77	1.6e-04	3.4e-03	SPIC	121599
ENSG00000233093	25.46	-2.39	0.64	-3.75	1.8e-04	3.7e-03	LINC00892	100128420
ENSG00000231858	1.96	-3.00	0.81	-3.72	2.0e-04	4.1e-03	LOC105373805	105373805
ENSG00000255582	2.27	-4.44	1.20	-3.72	2.0e-04	4.1e-03	OR10G2	26534
ENSG00000181126	226.48	-2.09	0.56	-3.71	2.1e-04	4.2e-03	HLA-V	352962
ENSG00000228495	12.87	-2.59	0.70	-3.71	2.1e-04	4.3e-03	LINC01013	100507254
ENSG00000255221	1.65	-3.96	1.07	-3.70	2.1e-04	4.3e-03	CARD17	440068
ENSG00000241163	47.41	-2.79	0.75	-3.70	2.2e-04	4.4e-03	LINC00877	285286
ENSG00000125726	34.17	-2.72	0.74	-3.69	2.2e-04	4.4e-03	CD70	970
ENSG00000185972	11.61	2.51	0.68	3.69	2.3e-04	4.5e-03	CCIN	881
ENSG00000269720	9.15	-2.25	0.61	-3.69	2.3e-04	4.5e-03	CCDC194	110806280
ENSG00000272666	17.64	-2.62	0.72	-3.66	2.5e-04	4.9e-03	LOC105373098	105373098
ENSG00000179088	30.18	-3.61	0.99	-3.66	2.5e-04	5.0e-03	C12orf42	374470
ENSG00000226935	5.19	-2.79	0.76	-3.65	2.6e-04	5.0e-03	LINC00161	118421
ENSG00000152766	26.41	-2.38	0.65	-3.65	2.7e-04	5.2e-03	ANKRD22	118932
ENSG00000110680	74.69	3.45	0.95	3.64	2.8e-04	5.4e-03	CALCA	796
ENSG00000261760	8.02	2.32	0.64	3.63	2.8e-04	5.5e-03	LOC100507334	100507334
ENSG00000054803	35.24	2.56	0.70	3.63	2.8e-04	5.5e-03	CBLN4	140689
ENSG00000188848	78.97	-3.31	0.91	-3.62	2.9e-04	5.6e-03	BEND4	389206
ENSG00000133063	151.67	-2.04	0.56	-3.62	3.0e-04	5.7e-03	CHIT1	1118
ENSG00000223914	9.48	-4.56	1.26	-3.62	3.0e-04	5.7e-03	LINC02471	105369734
ENSG00000167618	5.97	-3.02	0.84	-3.61	3.0e-04	5.8e-03	LAIR2	3904
ENSG00000170786	15.44	-2.41	0.67	-3.60	3.2e-04	6.1e-03	SDR16C5	195814
ENSG00000170128	11.45	-2.14	0.60	-3.59	3.3e-04	6.2e-03	GPR25	2848
ENSG00000105251	7.38	-2.29	0.64	-3.59	3.3e-04	6.2e-03	SHD	56961
ENSG00000100079	38.13	-2.31	0.64	-3.59	3.3e-04	6.2e-03	LGALS2	3957
ENSG00000168078	36.21	-2.07	0.58	-3.59	3.4e-04	6.3e-03	PBK	55872
ENSG00000164265	8.02	-2.56	0.72	-3.58	3.5e-04	6.5e-03	SCGB3A2	117156
ENSG00000137868	91.86	-2.26	0.64	-3.52	4.4e-04	7.9e-03	STRA6	64220
ENSG00000078081	359.38	-2.11	0.60	-3.50	4.6e-04	8.2e-03	LAMP3	27074
ENSG00000197721	7.85	-2.56	0.73	-3.50	4.6e-04	8.2e-03	CR1L	1379
ENSG00000254126	5.04	-3.46	0.99	-3.49	4.8e-04	8.5e-03	CD8B2	927
ENSG00000224184	4.39	-3.18	0.92	-3.45	5.6e-04	9.6e-03	MIR3681HG	100506457
ENSG00000258512	19.70	-2.01	0.58	-3.45	5.6e-04	9.7e-03	LINC00239	145200
ENSG00000158402	13.54	-2.05	0.59	-3.44	5.8e-04	9.9e-03	CDC25C	995
ENSG00000141096	12.75	-2.01	0.58	-3.44	5.8e-04	9.9e-03	DPEP3	64180
ENSG00000104970	16.91	-2.51	0.73	-3.44	5.8e-04	1.0e-02	KIR3DX1	90011
ENSG00000267123	4.99	-2.43	0.71	-3.41	6.4e-04	1.1e-02	SCAT1	101928710
ENSG00000258525	8.96	-2.09	0.61	-3.41	6.5e-04	1.1e-02	LOC100506071	100506071
ENSG00000255772	2.18	-3.11	0.91	-3.41	6.6e-04	1.1e-02	LINC01479	101927922
ENSG00000104951	86.11	-2.08	0.62	-3.38	7.2e-04	1.2e-02	IL4I1	259307
ENSG00000121570	9.87	-2.10	0.62	-3.38	7.3e-04	1.2e-02	DPPA4	55211
ENSG00000212658	1.64	-4.08	1.21	-3.36	7.7e-04	1.3e-02	KRTAP29-1	100533177
ENSG00000165509	26.92	2.14	0.64	3.35	8.1e-04	1.3e-02	MAGEC3	139081
ENSG00000214336	1.32	-3.50	1.05	-3.34	8.4e-04	1.4e-02	FOXI3	344167
ENSG00000169035	24.78	2.23	0.67	3.33	8.7e-04	1.4e-02	KLK7	5650
ENSG00000124635	129.01	-2.28	0.69	-3.31	9.5e-04	1.5e-02	H2BC11	8970
ENSG00000230023	1.36	-3.44	1.05	-3.29	1.0e-03	1.6e-02	LINC02800	284632
ENSG00000144481	4.46	-3.27	0.99	-3.28	1.0e-03	1.6e-02	TRPM8	79054
ENSG00000258869	1.21	-4.12	1.25	-3.28	1.0e-03	1.6e-02	LINC02312	100132612
ENSG00000136244	352.73	2.50	0.77	3.27	1.1e-03	1.6e-02	IL6	3569
ENSG00000135248	11.80	2.25	0.69	3.27	1.1e-03	1.7e-02	FAM71F1	84691
ENSG00000187033	1.31	-3.52	1.08	-3.27	1.1e-03	1.7e-02	SAMD7	344658
ENSG00000237541	438.68	-2.95	0.90	-3.26	1.1e-03	1.7e-02	HLA-DQA1	3117
ENSG00000249993	5.95	-2.93	0.90	-3.24	1.2e-03	1.8e-02	BFSP2-AS1	85003
ENSG00000140835	20.12	-2.01	0.62	-3.24	1.2e-03	1.8e-02	CHST4	10164
ENSG00000158050	1402.26	-2.46	0.76	-3.24	1.2e-03	1.8e-02	DUSP2	1844
ENSG00000183395	3.02	-3.14	0.97	-3.23	1.2e-03	1.9e-02	PMCH	5367
ENSG00000255151	2.16	-4.92	1.53	-3.23	1.3e-03	1.9e-02	GLYATL1B	100287520
ENSG00000205057	2.70	-5.30	1.65	-3.21	1.3e-03	2.0e-02	CLLU1OS	574016
ENSG00000254521	16.19	-2.01	0.63	-3.19	1.4e-03	2.1e-02	SIGLEC12	89858
ENSG00000237372	2.31	-4.12	1.29	-3.19	1.4e-03	2.1e-02	UNQ6494	100129066
ENSG00000168594	2.96	-3.82	1.20	-3.18	1.5e-03	2.1e-02	ADAM29	11086
ENSG00000159516	2.32	3.23	1.03	3.15	1.6e-03	2.3e-02	SPRR2G	6706
ENSG00000111536	3.73	-3.02	0.96	-3.14	1.7e-03	2.3e-02	IL26	55801
ENSG00000233392	29.01	-2.34	0.75	-3.14	1.7e-03	2.4e-02	LOC200772	200772
ENSG00000116031	37.13	-2.50	0.80	-3.11	1.9e-03	2.6e-02	CD207	50489
ENSG00000124575	42.22	-2.83	0.91	-3.11	1.9e-03	2.6e-02	H1-3	3007
ENSG00000163501	96.72	2.65	0.85	3.10	1.9e-03	2.6e-02	IHH	3549
ENSG00000249534	3.17	2.54	0.82	3.09	2.0e-03	2.7e-02	LINC01258	101928776
ENSG00000138684	1.57	-4.14	1.34	-3.08	2.1e-03	2.8e-02	IL21	59067
ENSG00000130957	5.14	-2.27	0.74	-3.07	2.1e-03	2.8e-02	FBP2	8789
ENSG00000249667	1.64	-4.06	1.32	-3.07	2.1e-03	2.8e-02	LINC01259	106144599
ENSG00000133980	4.43	-3.23	1.05	-3.07	2.1e-03	2.9e-02	VRTN	55237
ENSG00000116014	6.12	-2.44	0.79	-3.07	2.2e-03	2.9e-02	KISS1R	84634
ENSG00000267593	1.37	-3.65	1.19	-3.06	2.2e-03	2.9e-02	LINC01926	105372147
ENSG00000124391	4.71	-2.37	0.77	-3.06	2.2e-03	2.9e-02	IL17C	27189
ENSG00000148123	1.49	3.28	1.07	3.06	2.2e-03	2.9e-02	PLPPR1	54886
ENSG00000185130	4.60	-2.84	0.93	-3.06	2.2e-03	2.9e-02	H2BC13	8340
ENSG00000267568	3.22	-2.60	0.85	-3.06	2.2e-03	2.9e-02	LOC105371899	105371899
ENSG00000173404	10.58	-2.66	0.87	-3.05	2.3e-03	3.0e-02	INSM1	3642
ENSG00000253214	2.27	-3.11	1.02	-3.05	2.3e-03	3.0e-02	LOC105375924	105375924
ENSG00000171643	10.08	-2.09	0.69	-3.05	2.3e-03	3.0e-02	S100Z	170591
ENSG00000092758	3756.11	2.13	0.70	3.04	2.4e-03	3.1e-02	COL9A3	1299
ENSG00000196890	19.23	-2.74	0.91	-3.03	2.5e-03	3.2e-02	H2BU1	128312
ENSG00000154165	59.57	-2.65	0.88	-3.02	2.5e-03	3.2e-02	GPR15	2838
ENSG00000128322	10.47	-2.10	0.70	-3.00	2.7e-03	3.4e-02	IGLL1	3543
ENSG00000230943	3.19	-3.58	1.20	-3.00	2.7e-03	3.4e-02	LINC02541	101927686
ENSG00000150275	13.55	-2.45	0.82	-2.99	2.8e-03	3.5e-02	PCDH15	65217
ENSG00000187848	33.72	-2.99	1.00	-2.99	2.8e-03	3.5e-02	P2RX2	22953
ENSG00000265929	1.00	-3.92	1.31	-2.99	2.8e-03	3.5e-02	MIR5195	100847062
ENSG00000247151	2.16	-2.90	0.97	-2.99	2.8e-03	3.5e-02	CSTF3-DT	338739
ENSG00000226397	2.11	-3.58	1.20	-2.98	2.9e-03	3.6e-02	C12orf77	196415
ENSG00000208024	2.71	2.06	0.69	2.97	3.0e-03	3.7e-02	MIR199A2	406977
ENSG00000197153	5.52	-2.56	0.87	-2.96	3.1e-03	3.7e-02	H3C12	8356
ENSG00000101292	2.26	-3.86	1.31	-2.96	3.1e-03	3.8e-02	PROKR2	128674
ENSG00000163121	5.59	-2.34	0.79	-2.95	3.1e-03	3.8e-02	NEURL3	93082
ENSG00000203814	172.27	-2.37	0.80	-2.95	3.2e-03	3.8e-02	H2BC18	440689
ENSG00000197888	9.89	-2.58	0.88	-2.94	3.3e-03	3.9e-02	UGT2B17	7367
ENSG00000164400	2.17	-3.70	1.26	-2.94	3.3e-03	4.0e-02	CSF2	1437
ENSG00000184357	4.57	-3.23	1.11	-2.91	3.6e-03	4.2e-02	H1-5	3009
ENSG00000105352	40.06	-2.10	0.72	-2.91	3.6e-03	4.2e-02	CEACAM4	1089
ENSG00000175514	3.17	-2.31	0.80	-2.89	3.9e-03	4.4e-02	GPR152	390212
ENSG00000185736	31.46	-2.17	0.75	-2.89	3.9e-03	4.4e-02	ADARB2	105
ENSG00000226807	7.26	2.29	0.79	2.89	3.9e-03	4.4e-02	MROH5	389690
ENSG00000231787	1.37	-3.44	1.20	-2.87	4.1e-03	4.6e-02	H2BP9	115482691
ENSG00000090402	1.65	4.03	1.41	2.87	4.1e-03	4.7e-02	SI	6476
ENSG00000139151	1.34	-2.97	1.04	-2.86	4.2e-03	4.7e-02	PLCZ1	89869
ENSG00000016490	3.87	2.20	0.77	2.86	4.2e-03	4.8e-02	CLCA1	1179
ENSG00000169248	73.15	-2.44	0.85	-2.86	4.2e-03	4.8e-02	CXCL11	6373
ENSG00000132437	9.84	2.53	0.89	2.84	4.5e-03	5.0e-02	DDC	1644
ENSG00000245928	1.96	-2.53	0.89	-2.83	4.6e-03	5.1e-02	LOC101928809	101928809
ENSG00000183822	3.41	-2.28	0.81	-2.83	4.7e-03	5.1e-02	NCF4-AS1	107985578
ENSG00000267522	1.81	2.63	0.93	2.81	4.9e-03	5.3e-02	LINC01864	101928886
ENSG00000135903	2.76	2.27	0.81	2.80	5.1e-03	5.4e-02	PAX3	5077
ENSG00000254415	110.45	-2.15	0.77	-2.80	5.1e-03	5.5e-02	SIGLEC14	100049587
ENSG00000138483	9.97	2.09	0.75	2.79	5.2e-03	5.6e-02	CCDC54	84692
ENSG00000207205	0.91	-2.71	0.97	-2.78	5.4e-03	5.7e-02	RNVU1-15	101954267
ENSG00000147256	4.77	2.12	0.76	2.78	5.4e-03	5.7e-02	ARHGAP36	158763
ENSG00000075461	19.72	2.12	0.77	2.77	5.5e-03	5.8e-02	CACNG4	27092
ENSG00000258483	2.19	-3.44	1.24	-2.77	5.6e-03	5.9e-02	LINC02251	105371008
ENSG00000176177	3.53	-2.64	0.95	-2.77	5.7e-03	5.9e-02	ENTHD1	150350
ENSG00000139223	1.35	3.42	1.24	2.76	5.9e-03	6.0e-02	ANP32D	23519
ENSG00000131142	6.76	-2.16	0.79	-2.74	6.1e-03	6.3e-02	CCL25	6370
ENSG00000234224	5.03	2.81	1.03	2.73	6.2e-03	6.3e-02	TMEM229A	730130
ENSG00000137270	5.81	-2.58	0.95	-2.73	6.4e-03	6.4e-02	GCM1	8521
ENSG00000251676	3.18	3.06	1.12	2.73	6.4e-03	6.4e-02	SNHG27	101927305
ENSG00000145451	4.39	-2.86	1.05	-2.72	6.6e-03	6.5e-02	GLRA3	8001
ENSG00000229921	2.58	-2.32	0.86	-2.70	6.8e-03	6.7e-02	KIF25-AS1	100505879
ENSG00000197978	3.23	2.52	0.93	2.70	6.9e-03	6.8e-02	GOLGA6L9	440295
ENSG00000196131	1.19	2.95	1.09	2.69	7.1e-03	6.9e-02	VN1R2	317701
ENSG00000189099	1.17	2.41	0.89	2.69	7.1e-03	6.9e-02	PRSS48	345062
ENSG00000147570	13.76	-2.33	0.86	-2.69	7.1e-03	6.9e-02	DNAJC5B	85479
ENSG00000249550	1.89	-3.38	1.26	-2.69	7.2e-03	7.0e-02	LINC01234	100506465
ENSG00000186844	1.39	3.03	1.13	2.68	7.3e-03	7.1e-02	LCE1A	353131
ENSG00000115602	1073.94	2.42	0.90	2.68	7.3e-03	7.1e-02	IL1RL1	9173
ENSG00000204033	2.20	-2.46	0.92	-2.68	7.4e-03	7.1e-02	LRIT2	340745
ENSG00000180613	1.49	-3.93	1.47	-2.68	7.4e-03	7.1e-02	GSX2	170825
ENSG00000137561	2.22	-2.12	0.80	-2.66	7.8e-03	7.4e-02	TTPA	7274
ENSG00000198685	0.88	2.90	1.10	2.64	8.3e-03	7.8e-02	LINC01565	23434
ENSG00000254233	1.27	-3.56	1.35	-2.63	8.4e-03	7.8e-02	LINC02365	105377586
ENSG00000106302	6.53	-2.51	0.95	-2.63	8.4e-03	7.8e-02	HYAL4	23553
ENSG00000086967	152.58	-2.00	0.77	-2.62	8.8e-03	8.1e-02	MYBPC2	4606
ENSG00000215182	8.42	2.27	0.87	2.62	8.9e-03	8.2e-02	MUC5AC	4586
ENSG00000226806	1.82	-4.81	1.85	-2.60	9.3e-03	8.4e-02	LCT-AS1	100507600
ENSG00000261645	1.22	-2.76	1.08	-2.57	1.0e-02	9.0e-02	DISC1FP1	101929222
ENSG00000218819	1.27	-4.02	1.57	-2.56	1.0e-02	9.0e-02	TDRD15	100129278
ENSG00000152592	4.89	2.01	0.79	2.55	1.1e-02	9.3e-02	DMP1	1758
ENSG00000173213	16.65	-2.07	0.81	-2.55	1.1e-02	9.3e-02	TUBB8B	260334
ENSG00000258499	1.04	-3.29	1.29	-2.55	1.1e-02	9.4e-02	LINC02287	101929002
ENSG00000233922	1.78	-2.15	0.84	-2.55	1.1e-02	9.4e-02	LINC01694	105372840
ENSG00000167941	6.06	2.03	0.80	2.54	1.1e-02	9.4e-02	SOST	50964
ENSG00000089225	237.40	2.36	0.93	2.54	1.1e-02	9.4e-02	TBX5	6910
ENSG00000152430	3.77	2.31	0.91	2.54	1.1e-02	9.5e-02	BOLL	66037
ENSG00000240403	3.80	-2.75	1.08	-2.54	1.1e-02	9.6e-02	KIR3DL2	3812
ENSG00000229425	2.40	-2.61	1.03	-2.53	1.1e-02	9.7e-02	LOC101927745	101927745
ENSG00000228016	2.31	-2.11	0.84	-2.53	1.2e-02	9.8e-02	RAPGEF4-AS1	91149

out of 46777 with nonzero total read count
adjusted p-value < 0.1
LFC > 0 (up)       : 952, 2%
LFC < 0 (down)     : 2862, 6.1%
outliers [1]       : 0, 0%
low counts [2]     : 14515, 31%
(mean count < 1)
[1] see 'cooksCutoff' argument of ?results
[2] see 'independentFiltering' argument of ?results

Tabla 8: toptable y tabla resumen que contienen tanto la lista como el resumen de los genes que presentan evidencia de estar diferencialmente expresados entre las condiciones NIT y ELI.

SFI vs ELI:

Finalmente, vamos a estudiar que diferencias existen entre la presencia de infilitraciones focales y la presencia de infiltraciones extensivas. Análogamente a las dos comparaciones anteriores, en la Tabla 9 podemos viusalizar la topTable con los genes diferencialmente expresados entre condiciones y la summaryTable con un resumen del número de genes sobrexpresados e infraexpresados. Observamos que -respecto a la aplcación de infiltraciones focales- la aplicación de infilitraciones extensivas en el tejido tiroideo (ELI) desencadena una respuesta que implica -por lo menos- la expresión diferencial de 3814 (8.1%). De estos genes, un 2% están sobrexpresados y un 6.1% infraexpresados.

	baseMean	log2FoldChange	lfcSE	stat	pvalue	padj	symbol	entrez
ENSG00000105369	1948.87	-4.90	0.80	-6.14	8.4e-10	4.6e-07	CD79A	973
ENSG00000170476	1628.40	-4.15	0.74	-5.61	2.0e-08	7.4e-06	MZB1	51237
ENSG00000156738	5112.78	-4.50	0.81	-5.54	3.0e-08	1.0e-05	MS4A1	931
ENSG00000181847	505.03	-3.02	0.55	-5.52	3.3e-08	1.1e-05	TIGIT	201633
ENSG00000156234	561.78	-4.44	0.83	-5.32	1.0e-07	3.0e-05	CXCL13	10563
ENSG00000110777	1986.24	-3.24	0.62	-5.19	2.1e-07	5.7e-05	POU2AF1	5450
ENSG00000226777	416.84	-3.91	0.76	-5.13	2.8e-07	7.5e-05	FAM30A	9834
ENSG00000132465	7603.68	-3.78	0.74	-5.09	3.6e-07	9.1e-05	JCHAIN	3512
ENSG00000129204	428.14	2.15	0.44	4.89	1.0e-06	2.4e-04	USP6	9098
ENSG00000187862	90.87	-2.94	0.60	-4.86	1.2e-06	2.7e-04	TTC24	164118
ENSG00000235304	36.49	-5.87	1.24	-4.74	2.1e-06	4.8e-04	LINC01281	286442
ENSG00000048462	108.47	-2.52	0.54	-4.68	2.8e-06	6.3e-04	TNFRSF17	608
ENSG00000163534	804.39	-3.53	0.76	-4.63	3.7e-06	8.2e-04	FCRL1	115350
ENSG00000160856	926.56	-3.03	0.66	-4.57	4.8e-06	1.0e-03	FCRL3	115352
ENSG00000177455	1184.57	-3.51	0.77	-4.56	5.1e-06	1.1e-03	CD19	930
ENSG00000254709	101.05	-4.44	0.98	-4.54	5.6e-06	1.1e-03	IGLL5	100423062
ENSG00000122188	236.81	-2.19	0.49	-4.51	6.6e-06	1.3e-03	LAX1	54900
ENSG00000235532	73.30	-4.17	0.93	-4.51	6.6e-06	1.3e-03	LINC00402	100507612
ENSG00000026751	787.52	-2.25	0.50	-4.49	7.2e-06	1.4e-03	SLAMF7	57823
ENSG00000197057	177.97	-2.42	0.54	-4.45	8.5e-06	1.7e-03	DTHD1	401124
ENSG00000086967	152.58	-3.35	0.76	-4.38	1.2e-05	2.3e-03	MYBPC2	4606
ENSG00000136573	911.22	-2.90	0.66	-4.38	1.2e-05	2.3e-03	BLK	640
ENSG00000083454	913.26	-2.62	0.60	-4.37	1.2e-05	2.3e-03	P2RX5	5026
ENSG00000140465	120.99	-3.68	0.84	-4.36	1.3e-05	2.4e-03	CYP1A1	1543
ENSG00000089012	258.32	-2.24	0.51	-4.36	1.3e-05	2.4e-03	SIRPG	55423
ENSG00000121895	207.04	-2.60	0.60	-4.32	1.5e-05	2.8e-03	TMEM156	80008
ENSG00000196092	398.98	-3.43	0.80	-4.31	1.6e-05	2.8e-03	PAX5	5079
ENSG00000159958	162.27	-3.54	0.82	-4.30	1.7e-05	3.0e-03	TNFRSF13C	115650
ENSG00000122224	497.02	-2.47	0.58	-4.28	1.8e-05	3.2e-03	LY9	4063
ENSG00000143297	1671.07	-3.42	0.80	-4.27	2.0e-05	3.4e-03	FCRL5	83416
ENSG00000113088	259.07	-2.48	0.58	-4.26	2.0e-05	3.4e-03	GZMK	3003
ENSG00000116748	50.56	-2.34	0.55	-4.24	2.2e-05	3.7e-03	AMPD1	270
ENSG00000198576	199.58	2.48	0.59	4.18	2.9e-05	4.7e-03	ARC	23237
ENSG00000086159	5.21	2.72	0.66	4.13	3.6e-05	5.6e-03	AQP6	363
ENSG00000138755	1841.40	-2.50	0.61	-4.13	3.6e-05	5.7e-03	CXCL9	4283
ENSG00000168081	68.51	-2.60	0.64	-4.07	4.7e-05	7.1e-03	PNOC	5368
ENSG00000092345	4.26	4.26	1.07	3.97	7.0e-05	1.0e-02	DAZL	1618
ENSG00000257242	72.86	-2.07	0.52	-3.96	7.5e-05	1.1e-02	LINC01619	256021
ENSG00000240505	194.19	-4.25	1.08	-3.92	8.7e-05	1.2e-02	TNFRSF13B	23495
ENSG00000131096	18.83	2.26	0.58	3.91	9.2e-05	1.3e-02	PYY	5697
ENSG00000165076	9.47	2.28	0.59	3.89	1.0e-04	1.4e-02	PRSS37	136242
ENSG00000225362	35.25	2.07	0.54	3.85	1.2e-04	1.6e-02	CT62	196993
ENSG00000183918	263.35	-2.09	0.54	-3.85	1.2e-04	1.6e-02	SH2D1A	4068
ENSG00000255760	66.56	-4.18	1.09	-3.84	1.2e-04	1.6e-02	LINC02422	105369723
ENSG00000269404	416.45	-2.45	0.64	-3.82	1.3e-04	1.8e-02	SPIB	6689
ENSG00000171903	519.64	-2.20	0.58	-3.80	1.5e-04	1.9e-02	CYP4F11	57834
ENSG00000234184	32.14	-4.48	1.18	-3.79	1.5e-04	2.0e-02	LINC01781	101927412
ENSG00000178562	397.88	-2.24	0.60	-3.76	1.7e-04	2.1e-02	CD28	940
ENSG00000136931	7.75	2.98	0.80	3.73	1.9e-04	2.4e-02	NR5A1	2516
ENSG00000158477	22.99	-3.95	1.07	-3.70	2.2e-04	2.7e-02	CD1A	909
ENSG00000137673	23.60	-2.89	0.78	-3.69	2.2e-04	2.7e-02	MMP7	4316
ENSG00000135248	11.80	2.57	0.70	3.68	2.3e-04	2.8e-02	FAM71F1	84691
ENSG00000102970	22.77	-3.33	0.91	-3.65	2.6e-04	3.1e-02	CCL17	6361
ENSG00000049249	22.64	-2.35	0.65	-3.64	2.8e-04	3.3e-02	TNFRSF9	3604
ENSG00000249923	7.03	2.03	0.56	3.62	3.0e-04	3.5e-02	LOC284865	284865
ENSG00000255733	55.44	-2.68	0.75	-3.55	3.9e-04	4.4e-02	IFNG-AS1	100885789
ENSG00000185972	11.61	2.40	0.68	3.52	4.2e-04	4.7e-02	CCIN	881
ENSG00000163599	420.70	-2.19	0.63	-3.49	4.9e-04	5.4e-02	CTLA4	1493
ENSG00000254211	7.61	-2.54	0.73	-3.47	5.2e-04	5.6e-02	LINC01485	101928154
ENSG00000078589	193.96	-2.04	0.59	-3.47	5.3e-04	5.7e-02	P2RY10	27334
ENSG00000234572	10.73	-3.91	1.14	-3.44	5.8e-04	6.0e-02	LINC01800	101927438
ENSG00000163508	258.50	-2.01	0.58	-3.44	5.9e-04	6.1e-02	EOMES	8320
ENSG00000169245	334.62	-2.56	0.75	-3.43	6.1e-04	6.3e-02	CXCL10	3627
ENSG00000159556	10.15	-2.90	0.85	-3.40	6.7e-04	6.8e-02	ISL2	64843
ENSG00000256574	14.46	-3.47	1.02	-3.39	6.9e-04	6.9e-02	OR13A1	79290
ENSG00000231439	54.87	2.28	0.68	3.34	8.3e-04	8.0e-02	WASIR2	100132169
ENSG00000144460	7.44	-3.25	0.98	-3.33	8.6e-04	8.2e-02	NYAP2	57624
ENSG00000100721	310.88	-3.08	0.93	-3.30	9.6e-04	8.9e-02	TCL1A	8115
ENSG00000204595	1.65	3.59	1.09	3.29	9.9e-04	9.2e-02	DPRX	503834
ENSG00000185155	28.43	-2.44	0.75	-3.27	1.1e-03	9.9e-02	MIXL1	83881

out of 46777 with nonzero total read count
adjusted p-value < 0.1
LFC > 0 (up)       : 1292, 2.8%
LFC < 0 (down)     : 2843, 6.1%
outliers [1]       : 0, 0%
low counts [2]     : 17235, 37%
(mean count < 2)
[1] see 'cooksCutoff' argument of ?results
[2] see 'independentFiltering' argument of ?results

Tabla 9: toptable y tabla resumen que contienen tanto la lista como el resumen de los genes que presentan evidencia de estar diferencialmente expresados entre las condiciones SFI y ELI.

Las tablas de genes diferencialmente expresados (conocidas también como topTables) tienen la misma debilidad y el mismo punto fuerte: contienen demasiada información. Una alternativa más visual para identificar cuan diferencialmente expresados están los genes de cada comparación es mediante el uso de volcano plots. A continuación se muestran los volcano plots para cada una de las 3 comparaciones (Figura 3). Para facilitar su interpretación se han añadido una línea horizontal con el fdr cutoff (FDR = 0.1), dos líneas verticales con los foldChange cutoffs (FC = -2, 2) y una leyenda de colores (NS = gris, log2FC = verde, p-value = azul, p-value & log2FC = rojo).

En línea con lo observado en las topTables y las summaryTables, los volcano plots parecen indicar que las comparaciones que presentan una mayor variación en su expresión son NITvsELI y SFIvsELI. Visto de otro modo, esto sugiere que la aplicación de infiltraciones focales no tiene un efecto demasiado significativo respecto al control. Estos resultados secundan el patrón que observamos en el PCA plot de los datos normalizados (Figura 1).

Figura 3: volcano plots resultantes de las comparaciones entre los grupos NIT, SFI (A), NIT y ELI (B) y SFI y ELI (C). Se consideran diferencialmente expresados los genes que corresponden a los puntos de color rojo.

Análisis de significación

Aunque ya conocemos que genes están sobrexpresados o infraexpresados en cada de las comparaciones, es difícil extraer conclusiones a partir de esta información. Con el objetivo de obtener una visión más general e identificar que vías metabólicas se ven modificadas por la presencia y grado de infiltraciones en el tejido tiroideo, podemos realizar un análisis de significación o de pathways. Este tipo de análisis permiten clasificar y agrupar los genes diferencialmente expresados dentro de las vías metabólicas en las que participan. A continuación se muestra, para cada dieta, una tabla que contiene los resultados de este análisis (Tablas 10-12).

NIT vs SFI:

	Description	GeneRatio	BgRatio	pvalue	p.adjust	qvalue
GO:0042113	B cell activation	12/54	310/18670	6.5e-11	6.6e-08	4.9e-08
GO:0042100	B cell proliferation	8/54	95/18670	2.9e-10	1.4e-07	1.1e-07
GO:0050853	B cell receptor signaling pathway	8/54	129/18670	3.3e-09	1.1e-06	8.4e-07
GO:0006959	humoral immune response	11/54	356/18670	4.8e-09	1.2e-06	9.0e-07
GO:0050851	antigen receptor-mediated signaling pathway	10/54	316/18670	2.1e-08	4.2e-06	3.1e-06
GO:0050864	regulation of B cell activation	8/54	184/18670	5.4e-08	9.1e-06	6.8e-06
GO:0046651	lymphocyte proliferation	9/54	272/18670	7.8e-08	1.0e-05	7.8e-06
GO:0032943	mononuclear cell proliferation	9/54	274/18670	8.3e-08	1.0e-05	7.8e-06
GO:0051249	regulation of lymphocyte activation	11/54	485/18670	1.1e-07	1.3e-05	9.5e-06
GO:0070661	leukocyte proliferation	9/54	298/18670	1.7e-07	1.7e-05	1.3e-05
GO:0002429	immune response-activating cell surface receptor signaling pathway	10/54	473/18670	8.7e-07	7.4e-05	5.5e-05
GO:0030888	regulation of B cell proliferation	5/54	61/18670	8.8e-07	7.4e-05	5.5e-05
GO:0050855	regulation of B cell receptor signaling pathway	4/54	29/18670	1.4e-06	1.1e-04	8.2e-05
GO:0030098	lymphocyte differentiation	8/54	353/18670	7.4e-06	5.3e-04	4.0e-04
GO:0010524	positive regulation of calcium ion transport into cytosol	4/54	54/18670	1.8e-05	1.2e-03	8.9e-04
GO:0050670	regulation of lymphocyte proliferation	6/54	208/18670	2.9e-05	1.8e-03	1.3e-03
GO:0032944	regulation of mononuclear cell proliferation	6/54	209/18670	3.0e-05	1.8e-03	1.3e-03
GO:0007204	positive regulation of cytosolic calcium ion concentration	7/54	319/18670	3.5e-05	2.0e-03	1.5e-03
GO:0050854	regulation of antigen receptor-mediated signaling pathway	4/54	65/18670	3.7e-05	2.0e-03	1.5e-03
GO:0070663	regulation of leukocyte proliferation	6/54	222/18670	4.2e-05	2.1e-03	1.6e-03
GO:0042110	T cell activation	8/54	464/18670	5.2e-05	2.5e-03	1.9e-03
GO:0051480	regulation of cytosolic calcium ion concentration	7/54	357/18670	7.2e-05	3.3e-03	2.5e-03
GO:0002460	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	7/54	361/18670	7.7e-05	3.4e-03	2.5e-03
GO:0060402	calcium ion transport into cytosol	5/54	158/18670	9.2e-05	3.9e-03	2.9e-03
GO:0070098	chemokine-mediated signaling pathway	4/54	88/18670	1.2e-04	4.9e-03	3.7e-03
GO:0060401	cytosolic calcium ion transport	5/54	171/18670	1.3e-04	5.2e-03	3.9e-03
GO:0022407	regulation of cell-cell adhesion	7/54	403/18670	1.5e-04	5.7e-03	4.3e-03
GO:1990868	response to chemokine	4/54	97/18670	1.8e-04	6.2e-03	4.6e-03
GO:1990869	cellular response to chemokine	4/54	97/18670	1.8e-04	6.2e-03	4.6e-03
GO:0071356	cellular response to tumor necrosis factor	6/54	291/18670	1.9e-04	6.3e-03	4.7e-03
GO:0051281	positive regulation of release of sequestered calcium ion into cytosol	3/54	40/18670	2.1e-04	6.8e-03	5.1e-03
GO:0010522	regulation of calcium ion transport into cytosol	4/54	102/18670	2.2e-04	6.8e-03	5.1e-03
GO:0030593	neutrophil chemotaxis	4/54	104/18670	2.3e-04	7.1e-03	5.3e-03
GO:1903037	regulation of leukocyte cell-cell adhesion	6/54	304/18670	2.4e-04	7.1e-03	5.3e-03
GO:0034612	response to tumor necrosis factor	6/54	312/18670	2.7e-04	7.9e-03	5.9e-03
GO:0050863	regulation of T cell activation	6/54	314/18670	2.8e-04	7.9e-03	5.9e-03
GO:0006874	cellular calcium ion homeostasis	7/54	458/18670	3.3e-04	9.1e-03	6.8e-03
GO:1990266	neutrophil migration	4/54	118/18670	3.8e-04	1.0e-02	7.4e-03
GO:0051251	positive regulation of lymphocyte activation	6/54	334/18670	3.9e-04	1.0e-02	7.4e-03
GO:0055074	calcium ion homeostasis	7/54	471/18670	4.0e-04	1.0e-02	7.4e-03
GO:0007159	leukocyte cell-cell adhesion	6/54	337/18670	4.1e-04	1.0e-02	7.5e-03
GO:0019730	antimicrobial humoral response	4/54	122/18670	4.3e-04	1.0e-02	7.5e-03
GO:0051928	positive regulation of calcium ion transport	4/54	123/18670	4.4e-04	1.0e-02	7.5e-03
GO:0071621	granulocyte chemotaxis	4/54	123/18670	4.4e-04	1.0e-02	7.5e-03
GO:0045661	regulation of myoblast differentiation	3/54	53/18670	4.8e-04	1.1e-02	8.1e-03
GO:0002449	lymphocyte mediated immunity	6/54	352/18670	5.2e-04	1.1e-02	8.3e-03
GO:0072503	cellular divalent inorganic cation homeostasis	7/54	493/18670	5.2e-04	1.1e-02	8.3e-03
GO:0030183	B cell differentiation	4/54	131/18670	5.6e-04	1.2e-02	8.7e-03
GO:0031295	T cell costimulation	3/54	56/18670	5.7e-04	1.2e-02	8.7e-03
GO:0031294	lymphocyte costimulation	3/54	57/18670	6.0e-04	1.2e-02	9.0e-03
GO:0097530	granulocyte migration	4/54	141/18670	7.4e-04	1.4e-02	1.0e-02
GO:0050871	positive regulation of B cell activation	4/54	142/18670	7.6e-04	1.4e-02	1.0e-02
GO:0002260	lymphocyte homeostasis	3/54	62/18670	7.7e-04	1.4e-02	1.0e-02
GO:0002696	positive regulation of leukocyte activation	6/54	380/18670	7.7e-04	1.4e-02	1.0e-02
GO:1904064	positive regulation of cation transmembrane transport	4/54	144/18670	8.0e-04	1.4e-02	1.0e-02
GO:0002637	regulation of immunoglobulin production	3/54	63/18670	8.0e-04	1.4e-02	1.0e-02
GO:0051924	regulation of calcium ion transport	5/54	254/18670	8.2e-04	1.4e-02	1.0e-02
GO:0022409	positive regulation of cell-cell adhesion	5/54	255/18670	8.4e-04	1.4e-02	1.0e-02
GO:0051250	negative regulation of lymphocyte activation	4/54	146/18670	8.4e-04	1.4e-02	1.0e-02
GO:0048247	lymphocyte chemotaxis	3/54	64/18670	8.4e-04	1.4e-02	1.0e-02
GO:0002467	germinal center formation	2/54	15/18670	8.4e-04	1.4e-02	1.0e-02
GO:0050867	positive regulation of cell activation	6/54	394/18670	9.3e-04	1.5e-02	1.1e-02
GO:0030889	negative regulation of B cell proliferation	2/54	16/18670	9.6e-04	1.5e-02	1.1e-02
GO:2000243	positive regulation of reproductive process	3/54	69/18670	1.0e-03	1.7e-02	1.2e-02
GO:0034767	positive regulation of ion transmembrane transport	4/54	156/18670	1.1e-03	1.7e-02	1.2e-02
GO:0010819	regulation of T cell chemotaxis	2/54	17/18670	1.1e-03	1.7e-02	1.2e-02
GO:1904427	positive regulation of calcium ion transmembrane transport	3/54	71/18670	1.1e-03	1.7e-02	1.3e-02
GO:0043270	positive regulation of ion transport	5/54	275/18670	1.2e-03	1.7e-02	1.3e-02
GO:0061844	antimicrobial humoral immune response mediated by antimicrobial peptide	3/54	73/18670	1.2e-03	1.8e-02	1.3e-02
GO:0033209	tumor necrosis factor-mediated signaling pathway	4/54	167/18670	1.4e-03	2.0e-02	1.5e-02
GO:0007492	endoderm development	3/54	76/18670	1.4e-03	2.0e-02	1.5e-02
GO:0006816	calcium ion transport	6/54	434/18670	1.5e-03	2.2e-02	1.6e-02
GO:0002695	negative regulation of leukocyte activation	4/54	175/18670	1.6e-03	2.2e-02	1.7e-02
GO:0035590	purinergic nucleotide receptor signaling pathway	2/54	21/18670	1.7e-03	2.2e-02	1.7e-02
GO:1901739	regulation of myoblast fusion	2/54	21/18670	1.7e-03	2.2e-02	1.7e-02
GO:0051279	regulation of release of sequestered calcium ion into cytosol	3/54	82/18670	1.7e-03	2.3e-02	1.7e-02
GO:0033622	integrin activation	2/54	22/18670	1.8e-03	2.4e-02	1.8e-02
GO:0045445	myoblast differentiation	3/54	84/18670	1.8e-03	2.4e-02	1.8e-02
GO:0002285	lymphocyte activation involved in immune response	4/54	181/18670	1.9e-03	2.4e-02	1.8e-02
GO:0001776	leukocyte homeostasis	3/54	86/18670	2.0e-03	2.5e-02	1.9e-02
GO:0002697	regulation of immune effector process	6/54	458/18670	2.0e-03	2.5e-02	1.9e-02
GO:0002683	negative regulation of immune system process	6/54	463/18670	2.1e-03	2.6e-02	2.0e-02
GO:0002377	immunoglobulin production	4/54	193/18670	2.3e-03	2.8e-02	2.1e-02
GO:0032461	positive regulation of protein oligomerization	2/54	25/18670	2.4e-03	2.8e-02	2.1e-02
GO:0045662	negative regulation of myoblast differentiation	2/54	25/18670	2.4e-03	2.8e-02	2.1e-02
GO:0050866	negative regulation of cell activation	4/54	199/18670	2.6e-03	3.0e-02	2.3e-02
GO:0070838	divalent metal ion transport	6/54	483/18670	2.6e-03	3.0e-02	2.3e-02
GO:1901623	regulation of lymphocyte chemotaxis	2/54	27/18670	2.8e-03	3.1e-02	2.3e-02
GO:0050870	positive regulation of T cell activation	4/54	202/18670	2.8e-03	3.1e-02	2.3e-02
GO:0072511	divalent inorganic cation transport	6/54	489/18670	2.8e-03	3.1e-02	2.3e-02
GO:0034764	positive regulation of transmembrane transport	4/54	204/18670	2.9e-03	3.2e-02	2.4e-02
GO:0010818	T cell chemotaxis	2/54	28/18670	3.0e-03	3.3e-02	2.4e-02
GO:0002824	positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	3/54	100/18670	3.0e-03	3.3e-02	2.5e-02
GO:0050900	leukocyte migration	6/54	499/18670	3.1e-03	3.3e-02	2.5e-02
GO:0097529	myeloid leukocyte migration	4/54	210/18670	3.2e-03	3.3e-02	2.5e-02
GO:0060142	regulation of syncytium formation by plasma membrane fusion	2/54	29/18670	3.2e-03	3.3e-02	2.5e-02
GO:0001782	B cell homeostasis	2/54	30/18670	3.4e-03	3.5e-02	2.6e-02
GO:0050869	negative regulation of B cell activation	2/54	30/18670	3.4e-03	3.5e-02	2.6e-02
GO:0002708	positive regulation of lymphocyte mediated immunity	3/54	105/18670	3.5e-03	3.5e-02	2.6e-02
GO:0002821	positive regulation of adaptive immune response	3/54	105/18670	3.5e-03	3.5e-02	2.6e-02
GO:0002699	positive regulation of immune effector process	4/54	216/18670	3.5e-03	3.5e-02	2.6e-02
GO:2000406	positive regulation of T cell migration	2/54	31/18670	3.6e-03	3.6e-02	2.7e-02
GO:1903039	positive regulation of leukocyte cell-cell adhesion	4/54	218/18670	3.6e-03	3.6e-02	2.7e-02
GO:0001909	leukocyte mediated cytotoxicity	3/54	107/18670	3.7e-03	3.6e-02	2.7e-02
GO:0035587	purinergic receptor signaling pathway	2/54	32/18670	3.9e-03	3.7e-02	2.7e-02
GO:0045589	regulation of regulatory T cell differentiation	2/54	32/18670	3.9e-03	3.7e-02	2.7e-02
GO:0030595	leukocyte chemotaxis	4/54	224/18670	4.0e-03	3.8e-02	2.8e-02
GO:0072676	lymphocyte migration	3/54	111/18670	4.1e-03	3.8e-02	2.8e-02
GO:0050868	negative regulation of T cell activation	3/54	112/18670	4.2e-03	3.9e-02	2.9e-02
GO:0045066	regulatory T cell differentiation	2/54	34/18670	4.3e-03	4.0e-02	3.0e-02
GO:0032733	positive regulation of interleukin-10 production	2/54	36/18670	4.9e-03	4.4e-02	3.3e-02
GO:0030217	T cell differentiation	4/54	240/18670	5.1e-03	4.6e-02	3.4e-02
GO:2000403	positive regulation of lymphocyte migration	2/54	37/18670	5.1e-03	4.6e-02	3.4e-02
GO:0010959	regulation of metal ion transport	5/54	394/18670	5.5e-03	4.9e-02	3.6e-02
GO:0051209	release of sequestered calcium ion into cytosol	3/54	124/18670	5.5e-03	4.9e-02	3.6e-02

Tabla 10: GOtable que contiene las vías metabólicas expresadas diferencialmente entre los grupos NIT y SFI.

NIT vs ELI:

	Description	GeneRatio	BgRatio	pvalue	p.adjust	qvalue
GO:0042110	T cell activation	94/547	464/18670	3.6e-52	1.4e-48	1.2e-48
GO:0030098	lymphocyte differentiation	75/547	353/18670	4.9e-43	9.9e-40	8.1e-40
GO:0030217	T cell differentiation	58/547	240/18670	1.2e-36	1.7e-33	1.4e-33
GO:0051249	regulation of lymphocyte activation	78/547	485/18670	1.2e-35	1.1e-32	9.0e-33
GO:0050863	regulation of T cell activation	64/547	314/18670	1.4e-35	1.1e-32	9.0e-33
GO:0007159	leukocyte cell-cell adhesion	64/547	337/18670	1.1e-33	7.6e-31	6.3e-31
GO:1903037	regulation of leukocyte cell-cell adhesion	59/547	304/18670	1.3e-31	7.4e-29	6.1e-29
GO:1903039	positive regulation of leukocyte cell-cell adhesion	49/547	218/18670	1.8e-29	8.9e-27	7.3e-27
GO:0022407	regulation of cell-cell adhesion	63/547	403/18670	4.0e-28	1.8e-25	1.5e-25
GO:0050870	positive regulation of T cell activation	46/547	202/18670	5.4e-28	2.2e-25	1.8e-25
GO:0022409	positive regulation of cell-cell adhesion	50/547	255/18670	4.0e-27	1.5e-24	1.2e-24
GO:0046651	lymphocyte proliferation	50/547	272/18670	9.1e-26	3.1e-23	2.5e-23
GO:0070661	leukocyte proliferation	52/547	298/18670	1.2e-25	3.7e-23	3.1e-23
GO:0032943	mononuclear cell proliferation	50/547	274/18670	1.3e-25	3.7e-23	3.1e-23
GO:0002696	positive regulation of leukocyte activation	58/547	380/18670	2.1e-25	5.6e-23	4.6e-23
GO:0050867	positive regulation of cell activation	59/547	394/18670	2.2e-25	5.6e-23	4.6e-23
GO:0051251	positive regulation of lymphocyte activation	54/547	334/18670	6.2e-25	1.5e-22	1.2e-22
GO:0002449	lymphocyte mediated immunity	54/547	352/18670	8.4e-24	1.9e-21	1.5e-21
GO:0050670	regulation of lymphocyte proliferation	41/547	208/18670	1.7e-22	3.5e-20	2.9e-20
GO:0032944	regulation of mononuclear cell proliferation	41/547	209/18670	2.0e-22	4.0e-20	3.3e-20
GO:0070663	regulation of leukocyte proliferation	42/547	222/18670	2.6e-22	5.1e-20	4.2e-20
GO:0046631	alpha-beta T cell activation	34/547	138/18670	3.6e-22	6.7e-20	5.5e-20
GO:0045058	T cell selection	22/547	47/18670	9.2e-22	1.6e-19	1.3e-19
GO:0042113	B cell activation	48/547	310/18670	2.0e-21	3.3e-19	2.7e-19
GO:0045785	positive regulation of cell adhesion	54/547	403/18670	5.7e-21	9.1e-19	7.5e-19
GO:0050851	antigen receptor-mediated signaling pathway	47/547	316/18670	2.9e-20	4.5e-18	3.7e-18
GO:0045619	regulation of lymphocyte differentiation	35/547	169/18670	4.1e-20	5.9e-18	4.8e-18
GO:0002460	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	50/547	361/18670	4.1e-20	5.9e-18	4.8e-18
GO:0050900	leukocyte migration	59/547	499/18670	4.2e-20	5.9e-18	4.9e-18
GO:0043368	positive T cell selection	18/547	34/18670	2.7e-19	3.7e-17	3.0e-17
GO:0002429	immune response-activating cell surface receptor signaling pathway	56/547	473/18670	3.8e-19	5.0e-17	4.1e-17
GO:0002706	regulation of lymphocyte mediated immunity	32/547	149/18670	5.4e-19	6.8e-17	5.6e-17
GO:0046632	alpha-beta T cell differentiation	27/547	101/18670	7.4e-19	9.1e-17	7.5e-17
GO:0042129	regulation of T cell proliferation	32/547	156/18670	2.3e-18	2.7e-16	2.2e-16
GO:0002699	positive regulation of immune effector process	37/547	216/18670	2.9e-18	3.3e-16	2.7e-16
GO:1902105	regulation of leukocyte differentiation	41/547	272/18670	5.0e-18	5.6e-16	4.6e-16
GO:0045580	regulation of T cell differentiation	30/547	139/18670	5.9e-18	6.5e-16	5.3e-16
GO:0002697	regulation of immune effector process	53/547	458/18670	9.9e-18	1.1e-15	8.7e-16
GO:0002703	regulation of leukocyte mediated immunity	35/547	201/18670	1.4e-17	1.4e-15	1.2e-15
GO:0042102	positive regulation of T cell proliferation	25/547	95/18670	2.2e-17	2.3e-15	1.9e-15
GO:0042098	T cell proliferation	33/547	184/18670	4.8e-17	4.7e-15	3.9e-15
GO:0001819	positive regulation of cytokine production	52/547	464/18670	8.1e-17	7.8e-15	6.4e-15
GO:0002285	lymphocyte activation involved in immune response	32/547	181/18670	2.2e-16	2.1e-14	1.7e-14
GO:0002708	positive regulation of lymphocyte mediated immunity	25/547	105/18670	3.0e-16	2.7e-14	2.3e-14
GO:0070665	positive regulation of leukocyte proliferation	28/547	139/18670	5.2e-16	4.6e-14	3.8e-14
GO:0050671	positive regulation of lymphocyte proliferation	27/547	130/18670	7.7e-16	6.8e-14	5.6e-14
GO:0031295	T cell costimulation	19/547	56/18670	8.4e-16	7.3e-14	6.0e-14
GO:0032946	positive regulation of mononuclear cell proliferation	27/547	131/18670	9.5e-16	8.0e-14	6.5e-14
GO:0031294	lymphocyte costimulation	19/547	57/18670	1.2e-15	1.0e-13	8.4e-14
GO:0002683	negative regulation of immune system process	50/547	463/18670	1.5e-15	1.2e-13	9.9e-14
GO:0042100	B cell proliferation	23/547	95/18670	3.2e-15	2.5e-13	2.1e-13
GO:0033077	T cell differentiation in thymus	20/547	70/18670	6.4e-15	5.0e-13	4.1e-13
GO:0032609	interferon-gamma production	24/547	113/18670	1.9e-14	1.4e-12	1.2e-12
GO:0002819	regulation of adaptive immune response	28/547	160/18670	2.3e-14	1.7e-12	1.4e-12
GO:0031341	regulation of cell killing	22/547	98/18670	6.9e-14	5.0e-12	4.2e-12
GO:0002705	positive regulation of leukocyte mediated immunity	25/547	133/18670	1.0e-13	7.5e-12	6.1e-12
GO:0072676	lymphocyte migration	23/547	111/18670	1.2e-13	8.2e-12	6.7e-12
GO:0050852	T cell receptor signaling pathway	30/547	202/18670	2.4e-13	1.7e-11	1.4e-11
GO:0043367	CD4-positive, alpha-beta T cell differentiation	19/547	74/18670	2.6e-13	1.8e-11	1.5e-11
GO:0001909	leukocyte mediated cytotoxicity	22/547	107/18670	4.7e-13	3.2e-11	2.6e-11
GO:0031343	positive regulation of cell killing	18/547	68/18670	6.3e-13	4.2e-11	3.4e-11
GO:0001910	regulation of leukocyte mediated cytotoxicity	19/547	78/18670	7.3e-13	4.8e-11	3.9e-11
GO:0002822	regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	25/547	145/18670	8.0e-13	5.1e-11	4.2e-11
GO:0007204	positive regulation of cytosolic calcium ion concentration	37/547	319/18670	9.6e-13	6.1e-11	5.0e-11
GO:1903706	regulation of hemopoiesis	46/547	475/18670	1.1e-12	7.0e-11	5.7e-11
GO:0032649	regulation of interferon-gamma production	21/547	101/18670	1.3e-12	7.8e-11	6.4e-11
GO:0046634	regulation of alpha-beta T cell activation	20/547	93/18670	2.2e-12	1.4e-10	1.1e-10
GO:0045061	thymic T cell selection	11/547	21/18670	3.3e-12	2.0e-10	1.6e-10
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	16/547	56/18670	3.3e-12	2.0e-10	1.6e-10
GO:0001906	cell killing	26/547	168/18670	3.7e-12	2.1e-10	1.7e-10
GO:0030595	leukocyte chemotaxis	30/547	224/18670	3.7e-12	2.1e-10	1.7e-10
GO:1990868	response to chemokine	20/547	97/18670	5.2e-12	2.9e-10	2.3e-10
GO:1990869	cellular response to chemokine	20/547	97/18670	5.2e-12	2.9e-10	2.3e-10
GO:0051480	regulation of cytosolic calcium ion concentration	38/547	357/18670	6.7e-12	3.6e-10	3.0e-10
GO:0070098	chemokine-mediated signaling pathway	19/547	88/18670	7.4e-12	4.0e-10	3.3e-10
GO:0002695	negative regulation of leukocyte activation	26/547	175/18670	9.6e-12	5.1e-10	4.2e-10
GO:0035710	CD4-positive, alpha-beta T cell activation	19/547	92/18670	1.7e-11	9.0e-10	7.4e-10
GO:0046635	positive regulation of alpha-beta T cell activation	16/547	62/18670	1.9e-11	9.7e-10	7.9e-10
GO:0002440	production of molecular mediator of immune response	33/547	286/18670	1.9e-11	9.9e-10	8.1e-10
GO:0060326	cell chemotaxis	34/547	304/18670	2.3e-11	1.1e-09	9.4e-10
GO:0002821	positive regulation of adaptive immune response	20/547	105/18670	2.4e-11	1.2e-09	9.8e-10
GO:0045621	positive regulation of lymphocyte differentiation	19/547	94/18670	2.5e-11	1.3e-09	1.0e-09
GO:0002286	T cell activation involved in immune response	20/547	106/18670	2.9e-11	1.4e-09	1.2e-09
GO:1902107	positive regulation of leukocyte differentiation	23/547	144/18670	3.4e-11	1.6e-09	1.3e-09
GO:0032729	positive regulation of interferon-gamma production	16/547	65/18670	4.1e-11	1.9e-09	1.6e-09
GO:0042108	positive regulation of cytokine biosynthetic process	16/547	67/18670	6.7e-11	3.1e-09	2.6e-09
GO:0002824	positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	19/547	100/18670	7.9e-11	3.7e-09	3.0e-09
GO:0002377	immunoglobulin production	26/547	193/18670	9.0e-11	4.2e-09	3.4e-09
GO:0042035	regulation of cytokine biosynthetic process	20/547	114/18670	1.1e-10	5.2e-09	4.3e-09
GO:0055074	calcium ion homeostasis	42/547	471/18670	1.5e-10	6.9e-09	5.7e-09
GO:0050853	B cell receptor signaling pathway	21/547	129/18670	1.7e-10	7.4e-09	6.0e-09
GO:0002287	alpha-beta T cell activation involved in immune response	15/547	61/18670	1.7e-10	7.4e-09	6.0e-09
GO:0002293	alpha-beta T cell differentiation involved in immune response	15/547	61/18670	1.7e-10	7.4e-09	6.0e-09
GO:0050866	negative regulation of cell activation	26/547	199/18670	1.8e-10	7.7e-09	6.4e-09
GO:0002456	T cell mediated immunity	19/547	106/18670	2.3e-10	9.6e-09	7.9e-09
GO:0006874	cellular calcium ion homeostasis	41/547	458/18670	2.3e-10	9.6e-09	7.9e-09
GO:0043383	negative T cell selection	8/547	12/18670	2.3e-10	9.6e-09	7.9e-09
GO:0043373	CD4-positive, alpha-beta T cell lineage commitment	9/547	17/18670	2.9e-10	1.2e-08	1.0e-08
GO:0002228	natural killer cell mediated immunity	15/547	64/18670	3.5e-10	1.4e-08	1.2e-08
GO:0050854	regulation of antigen receptor-mediated signaling pathway	15/547	65/18670	4.5e-10	1.8e-08	1.5e-08
GO:0072678	T cell migration	15/547	65/18670	4.5e-10	1.8e-08	1.5e-08
GO:0042089	cytokine biosynthetic process	20/547	123/18670	4.7e-10	1.9e-08	1.5e-08
GO:0042107	cytokine metabolic process	20/547	124/18670	5.5e-10	2.1e-08	1.8e-08
GO:0002292	T cell differentiation involved in immune response	15/547	68/18670	8.8e-10	3.4e-08	2.8e-08
GO:0050864	regulation of B cell activation	24/547	184/18670	9.4e-10	3.6e-08	3.0e-08
GO:0002363	alpha-beta T cell lineage commitment	9/547	19/18670	1.1e-09	4.0e-08	3.3e-08
GO:0002294	CD4-positive, alpha-beta T cell differentiation involved in immune response	14/547	60/18670	1.5e-09	5.5e-08	4.5e-08
GO:0030183	B cell differentiation	20/547	131/18670	1.5e-09	5.5e-08	4.6e-08
GO:0002360	T cell lineage commitment	10/547	26/18670	1.5e-09	5.5e-08	4.6e-08
GO:0030888	regulation of B cell proliferation	14/547	61/18670	1.8e-09	6.8e-08	5.6e-08
GO:0043369	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	9/547	20/18670	1.9e-09	6.8e-08	5.6e-08
GO:0045582	positive regulation of T cell differentiation	16/547	83/18670	2.0e-09	7.2e-08	5.9e-08
GO:0072503	cellular divalent inorganic cation homeostasis	41/547	493/18670	2.1e-09	7.4e-08	6.1e-08
GO:0002237	response to molecule of bacterial origin	33/547	343/18670	2.3e-09	8.1e-08	6.7e-08
GO:0046637	regulation of alpha-beta T cell differentiation	14/547	63/18670	2.9e-09	1.0e-07	8.4e-08
GO:0006968	cellular defense response	13/547	53/18670	2.9e-09	1.0e-07	8.4e-08
GO:0032496	response to lipopolysaccharide	32/547	330/18670	3.3e-09	1.1e-07	9.4e-08
GO:0071219	cellular response to molecule of bacterial origin	25/547	212/18670	3.5e-09	1.2e-07	9.9e-08
GO:0002700	regulation of production of molecular mediator of immune response	20/547	139/18670	4.3e-09	1.5e-07	1.2e-07
GO:0045060	negative thymic T cell selection	7/547	11/18670	5.3e-09	1.8e-07	1.5e-07
GO:1903708	positive regulation of hemopoiesis	23/547	185/18670	5.4e-09	1.8e-07	1.5e-07
GO:0002295	T-helper cell lineage commitment	8/547	16/18670	5.4e-09	1.8e-07	1.5e-07
GO:0002715	regulation of natural killer cell mediated immunity	12/547	46/18670	5.6e-09	1.8e-07	1.5e-07
GO:0002381	immunoglobulin production involved in immunoglobulin mediated immune response	13/547	56/18670	6.1e-09	2.0e-07	1.6e-07
GO:0019722	calcium-mediated signaling	25/547	218/18670	6.3e-09	2.0e-07	1.7e-07
GO:0043370	regulation of CD4-positive, alpha-beta T cell differentiation	12/547	47/18670	7.3e-09	2.3e-07	1.9e-07
GO:0071216	cellular response to biotic stimulus	26/547	236/18670	7.3e-09	2.3e-07	1.9e-07
GO:0019724	B cell mediated immunity	25/547	221/18670	8.3e-09	2.6e-07	2.2e-07
GO:0071222	cellular response to lipopolysaccharide	24/547	205/18670	8.4e-09	2.6e-07	2.2e-07
GO:0042093	T-helper cell differentiation	13/547	58/18670	9.6e-09	3.0e-07	2.5e-07
GO:0051250	negative regulation of lymphocyte activation	20/547	146/18670	1.0e-08	3.1e-07	2.6e-07
GO:0072540	T-helper 17 cell lineage commitment	7/547	12/18670	1.2e-08	3.8e-07	3.1e-07
GO:0002709	regulation of T cell mediated immunity	14/547	70/18670	1.2e-08	3.8e-07	3.1e-07
GO:0042267	natural killer cell mediated cytotoxicity	13/547	60/18670	1.5e-08	4.5e-07	3.7e-07
GO:0002685	regulation of leukocyte migration	23/547	196/18670	1.6e-08	4.9e-07	4.0e-07
GO:0006959	humoral immune response	32/547	356/18670	2.1e-08	6.2e-07	5.1e-07
GO:0045059	positive thymic T cell selection	7/547	13/18670	2.6e-08	7.7e-07	6.4e-07
GO:0032103	positive regulation of response to external stimulus	30/547	323/18670	2.8e-08	8.1e-07	6.7e-07
GO:0045076	regulation of interleukin-2 biosynthetic process	8/547	19/18670	2.9e-08	8.5e-07	7.0e-07
GO:0019932	second-messenger-mediated signaling	36/547	439/18670	2.9e-08	8.5e-07	7.0e-07
GO:0042269	regulation of natural killer cell mediated cytotoxicity	11/547	44/18670	3.9e-08	1.1e-06	9.3e-07
GO:0045088	regulation of innate immune response	36/547	452/18670	6.1e-08	1.7e-06	1.4e-06
GO:0001773	myeloid dendritic cell activation	9/547	28/18670	6.3e-08	1.8e-06	1.5e-06
GO:0046638	positive regulation of alpha-beta T cell differentiation	11/547	47/18670	8.3e-08	2.3e-06	1.9e-06
GO:0042094	interleukin-2 biosynthetic process	8/547	22/18670	1.1e-07	3.2e-06	2.6e-06
GO:0016064	immunoglobulin mediated immune response	23/547	218/18670	1.2e-07	3.3e-06	2.7e-06
GO:0045954	positive regulation of natural killer cell mediated cytotoxicity	9/547	30/18670	1.2e-07	3.4e-06	2.8e-06
GO:2000514	regulation of CD4-positive, alpha-beta T cell activation	12/547	61/18670	1.7e-07	4.6e-06	3.7e-06
GO:0002312	B cell activation involved in immune response	13/547	73/18670	1.8e-07	4.8e-06	3.9e-06
GO:0001776	leukocyte homeostasis	14/547	86/18670	1.9e-07	5.1e-06	4.2e-06
GO:0032623	interleukin-2 production	12/547	62/18670	2.0e-07	5.4e-06	4.4e-06
GO:1903038	negative regulation of leukocyte cell-cell adhesion	17/547	129/18670	2.3e-07	6.1e-06	5.0e-06
GO:0002637	regulation of immunoglobulin production	12/547	63/18670	2.4e-07	6.4e-06	5.3e-06
GO:0050857	positive regulation of antigen receptor-mediated signaling pathway	8/547	24/18670	2.5e-07	6.6e-06	5.4e-06
GO:0002717	positive regulation of natural killer cell mediated immunity	9/547	33/18670	3.1e-07	7.9e-06	6.5e-06
GO:0032633	interleukin-4 production	9/547	33/18670	3.1e-07	7.9e-06	6.5e-06
GO:0050727	regulation of inflammatory response	36/547	485/18670	3.5e-07	8.9e-06	7.4e-06
GO:1990266	neutrophil migration	16/547	118/18670	3.5e-07	8.9e-06	7.4e-06
GO:0030593	neutrophil chemotaxis	15/547	104/18670	3.6e-07	9.1e-06	7.5e-06
GO:0050901	leukocyte tethering or rolling	8/547	25/18670	3.6e-07	9.1e-06	7.5e-06
GO:0032655	regulation of interleukin-12 production	11/547	54/18670	3.8e-07	9.4e-06	7.7e-06
GO:0032663	regulation of interleukin-2 production	11/547	54/18670	3.8e-07	9.4e-06	7.7e-06
GO:0022408	negative regulation of cell-cell adhesion	20/547	181/18670	3.8e-07	9.4e-06	7.7e-06
GO:0045066	regulatory T cell differentiation	9/547	34/18670	4.1e-07	1.0e-05	8.2e-06
GO:0050777	negative regulation of immune response	18/547	150/18670	4.2e-07	1.0e-05	8.6e-06
GO:0072539	T-helper 17 cell differentiation	8/547	26/18670	5.1e-07	1.2e-05	1.0e-05
GO:0032615	interleukin-12 production	11/547	56/18670	5.6e-07	1.3e-05	1.1e-05
GO:0045086	positive regulation of interleukin-2 biosynthetic process	6/547	13/18670	8.9e-07	2.1e-05	1.8e-05
GO:0050868	negative regulation of T cell activation	15/547	112/18670	9.5e-07	2.3e-05	1.9e-05
GO:0097529	myeloid leukocyte migration	21/547	210/18670	1.0e-06	2.4e-05	2.0e-05
GO:0002687	positive regulation of leukocyte migration	16/547	128/18670	1.1e-06	2.5e-05	2.1e-05
GO:0002688	regulation of leukocyte chemotaxis	15/547	114/18670	1.2e-06	2.8e-05	2.3e-05
GO:0002704	negative regulation of leukocyte mediated immunity	10/547	49/18670	1.3e-06	2.9e-05	2.4e-05
GO:0050855	regulation of B cell receptor signaling pathway	8/547	29/18670	1.3e-06	3.0e-05	2.4e-05
GO:0072538	T-helper 17 type immune response	8/547	29/18670	1.3e-06	3.0e-05	2.4e-05
GO:1903555	regulation of tumor necrosis factor superfamily cytokine production	18/547	163/18670	1.5e-06	3.3e-05	2.7e-05
GO:0046629	gamma-delta T cell activation	6/547	14/18670	1.5e-06	3.5e-05	2.8e-05
GO:0002260	lymphocyte homeostasis	11/547	62/18670	1.6e-06	3.6e-05	3.0e-05
GO:0002562	somatic diversification of immune receptors via germline recombination within a single locus	11/547	62/18670	1.6e-06	3.6e-05	3.0e-05
GO:0016444	somatic cell DNA recombination	11/547	62/18670	1.6e-06	3.6e-05	3.0e-05
GO:0032743	positive regulation of interleukin-2 production	8/547	30/18670	1.7e-06	3.8e-05	3.1e-05
GO:0043372	positive regulation of CD4-positive, alpha-beta T cell differentiation	8/547	30/18670	1.7e-06	3.8e-05	3.1e-05
GO:0002200	somatic diversification of immune receptors	12/547	75/18670	1.7e-06	3.8e-05	3.1e-05
GO:0002712	regulation of B cell mediated immunity	10/547	51/18670	1.9e-06	4.0e-05	3.3e-05
GO:0002889	regulation of immunoglobulin mediated immune response	10/547	51/18670	1.9e-06	4.0e-05	3.3e-05
GO:0034612	response to tumor necrosis factor	26/547	312/18670	1.9e-06	4.0e-05	3.3e-05
GO:2000401	regulation of lymphocyte migration	11/547	63/18670	1.9e-06	4.1e-05	3.4e-05
GO:0033209	tumor necrosis factor-mediated signaling pathway	18/547	167/18670	2.1e-06	4.5e-05	3.7e-05
GO:0048247	lymphocyte chemotaxis	11/547	64/18670	2.2e-06	4.8e-05	3.9e-05
GO:0071706	tumor necrosis factor superfamily cytokine production	18/547	168/18670	2.3e-06	4.8e-05	3.9e-05
GO:0001818	negative regulation of cytokine production	25/547	296/18670	2.3e-06	4.9e-05	4.0e-05
GO:0050663	cytokine secretion	22/547	240/18670	2.5e-06	5.2e-05	4.3e-05
GO:0050729	positive regulation of inflammatory response	17/547	153/18670	2.6e-06	5.5e-05	4.5e-05
GO:0097028	dendritic cell differentiation	9/547	42/18670	2.8e-06	5.8e-05	4.8e-05
GO:0032753	positive regulation of interleukin-4 production	7/547	23/18670	2.9e-06	6.0e-05	5.0e-05
GO:0045089	positive regulation of innate immune response	29/547	381/18670	3.0e-06	6.1e-05	5.0e-05
GO:0000819	sister chromatid segregation	19/547	189/18670	3.1e-06	6.3e-05	5.2e-05
GO:0007059	chromosome segregation	26/547	321/18670	3.1e-06	6.4e-05	5.3e-05
GO:0071621	granulocyte chemotaxis	15/547	123/18670	3.2e-06	6.4e-05	5.3e-05
GO:0140014	mitotic nuclear division	23/547	264/18670	3.5e-06	7.0e-05	5.8e-05
GO:0001914	regulation of T cell mediated cytotoxicity	8/547	33/18670	3.8e-06	7.5e-05	6.2e-05
GO:0000280	nuclear division	30/547	407/18670	3.8e-06	7.7e-05	6.3e-05
GO:0097530	granulocyte migration	16/547	141/18670	3.9e-06	7.7e-05	6.4e-05
GO:0033081	regulation of T cell differentiation in thymus	7/547	24/18670	4.0e-06	7.9e-05	6.5e-05
GO:0060402	calcium ion transport into cytosol	17/547	158/18670	4.1e-06	8.0e-05	6.6e-05
GO:2000404	regulation of T cell migration	9/547	44/18670	4.2e-06	8.3e-05	6.8e-05
GO:0032680	regulation of tumor necrosis factor production	17/547	160/18670	4.8e-06	9.4e-05	7.7e-05
GO:0006816	calcium ion transport	31/547	434/18670	5.0e-06	9.8e-05	8.1e-05
GO:0002820	negative regulation of adaptive immune response	9/547	45/18670	5.2e-06	1.0e-04	8.2e-05
GO:0071356	cellular response to tumor necrosis factor	24/547	291/18670	5.5e-06	1.1e-04	8.7e-05
GO:0006310	DNA recombination	24/547	292/18670	5.9e-06	1.1e-04	9.2e-05
GO:0002701	negative regulation of production of molecular mediator of immune response	8/547	35/18670	6.0e-06	1.1e-04	9.4e-05
GO:0045622	regulation of T-helper cell differentiation	8/547	35/18670	6.0e-06	1.1e-04	9.4e-05
GO:0032640	tumor necrosis factor production	17/547	163/18670	6.2e-06	1.2e-04	9.6e-05
GO:0002437	inflammatory response to antigenic stimulus	9/547	46/18670	6.2e-06	1.2e-04	9.6e-05
GO:0002204	somatic recombination of immunoglobulin genes involved in immune response	9/547	47/18670	7.5e-06	1.4e-04	1.1e-04
GO:0002208	somatic diversification of immunoglobulins involved in immune response	9/547	47/18670	7.5e-06	1.4e-04	1.1e-04
GO:0045190	isotype switching	9/547	47/18670	7.5e-06	1.4e-04	1.1e-04
GO:0030101	natural killer cell activation	12/547	86/18670	7.5e-06	1.4e-04	1.1e-04
GO:2000516	positive regulation of CD4-positive, alpha-beta T cell activation	8/547	36/18670	7.6e-06	1.4e-04	1.1e-04
GO:0002923	regulation of humoral immune response mediated by circulating immunoglobulin	5/547	11/18670	8.5e-06	1.5e-04	1.3e-04
GO:0033089	positive regulation of T cell differentiation in thymus	5/547	11/18670	8.5e-06	1.5e-04	1.3e-04
GO:0002690	positive regulation of leukocyte chemotaxis	12/547	87/18670	8.5e-06	1.5e-04	1.3e-04
GO:0002711	positive regulation of T cell mediated immunity	9/547	48/18670	9.0e-06	1.6e-04	1.3e-04
GO:0002714	positive regulation of B cell mediated immunity	8/547	37/18670	9.4e-06	1.7e-04	1.4e-04
GO:0002891	positive regulation of immunoglobulin mediated immune response	8/547	37/18670	9.4e-06	1.7e-04	1.4e-04
GO:0000070	mitotic sister chromatid segregation	16/547	151/18670	9.5e-06	1.7e-04	1.4e-04
GO:0032673	regulation of interleukin-4 production	7/547	27/18670	9.5e-06	1.7e-04	1.4e-04
GO:0034113	heterotypic cell-cell adhesion	10/547	61/18670	1.0e-05	1.8e-04	1.5e-04
GO:0045123	cellular extravasation	10/547	61/18670	1.0e-05	1.8e-04	1.5e-04
GO:0001913	T cell mediated cytotoxicity	9/547	49/18670	1.1e-05	1.9e-04	1.5e-04
GO:0071887	leukocyte apoptotic process	13/547	104/18670	1.1e-05	1.9e-04	1.6e-04
GO:0060401	cytosolic calcium ion transport	17/547	171/18670	1.2e-05	2.0e-04	1.7e-04
GO:0002922	positive regulation of humoral immune response	6/547	19/18670	1.2e-05	2.1e-04	1.7e-04
GO:0046641	positive regulation of alpha-beta T cell proliferation	6/547	19/18670	1.2e-05	2.1e-04	1.7e-04
GO:0071674	mononuclear cell migration	12/547	90/18670	1.2e-05	2.1e-04	1.7e-04
GO:0045577	regulation of B cell differentiation	7/547	28/18670	1.2e-05	2.1e-04	1.7e-04
GO:0048872	homeostasis of number of cells	21/547	246/18670	1.3e-05	2.1e-04	1.8e-04
GO:0002863	positive regulation of inflammatory response to antigenic stimulus	5/547	12/18670	1.4e-05	2.4e-04	2.0e-04
GO:0007162	negative regulation of cell adhesion	23/547	289/18670	1.5e-05	2.6e-04	2.1e-04
GO:0016445	somatic diversification of immunoglobulins	10/547	64/18670	1.6e-05	2.6e-04	2.2e-04
GO:0045165	cell fate commitment	22/547	270/18670	1.6e-05	2.7e-04	2.2e-04
GO:0051209	release of sequestered calcium ion into cytosol	14/547	124/18670	1.6e-05	2.7e-04	2.2e-04
GO:0070838	divalent metal ion transport	32/547	483/18670	1.6e-05	2.7e-04	2.2e-04
GO:0002823	negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	8/547	40/18670	1.7e-05	2.9e-04	2.4e-04
GO:0016447	somatic recombination of immunoglobulin gene segments	9/547	52/18670	1.8e-05	2.9e-04	2.4e-04
GO:0002548	monocyte chemotaxis	10/547	65/18670	1.8e-05	3.0e-04	2.4e-04
GO:0050871	positive regulation of B cell activation	15/547	142/18670	1.9e-05	3.0e-04	2.5e-04
GO:0051283	negative regulation of sequestering of calcium ion	14/547	126/18670	2.0e-05	3.2e-04	2.6e-04
GO:0050869	negative regulation of B cell activation	7/547	30/18670	2.0e-05	3.3e-04	2.7e-04
GO:0072511	divalent inorganic cation transport	32/547	489/18670	2.1e-05	3.4e-04	2.8e-04
GO:0051282	regulation of sequestering of calcium ion	14/547	128/18670	2.4e-05	3.8e-04	3.1e-04
GO:0048285	organelle fission	30/547	449/18670	2.6e-05	4.1e-04	3.4e-04
GO:2000106	regulation of leukocyte apoptotic process	11/547	83/18670	3.0e-05	4.7e-04	3.9e-04
GO:0051208	sequestering of calcium ion	14/547	131/18670	3.1e-05	4.9e-04	4.0e-04
GO:0048305	immunoglobulin secretion	6/547	22/18670	3.1e-05	4.9e-04	4.0e-04
GO:0045589	regulation of regulatory T cell differentiation	7/547	32/18670	3.2e-05	5.0e-04	4.1e-04
GO:0098813	nuclear chromosome segregation	21/547	262/18670	3.2e-05	5.0e-04	4.2e-04
GO:0002718	regulation of cytokine production involved in immune response	11/547	84/18670	3.3e-05	5.2e-04	4.3e-04
GO:0043374	CD8-positive, alpha-beta T cell differentiation	5/547	14/18670	3.4e-05	5.3e-04	4.3e-04
GO:0050862	positive regulation of T cell receptor signaling pathway	5/547	14/18670	3.4e-05	5.3e-04	4.3e-04
GO:0061756	leukocyte adhesion to vascular endothelial cell	8/547	44/18670	3.6e-05	5.6e-04	4.6e-04
GO:0046633	alpha-beta T cell proliferation	7/547	33/18670	3.9e-05	6.0e-04	5.0e-04
GO:0036037	CD8-positive, alpha-beta T cell activation	6/547	23/18670	4.1e-05	6.2e-04	5.1e-04
GO:0050921	positive regulation of chemotaxis	14/547	135/18670	4.3e-05	6.6e-04	5.4e-04
GO:0002532	production of molecular mediator involved in inflammatory response	10/547	72/18670	4.5e-05	6.8e-04	5.6e-04
GO:0032660	regulation of interleukin-17 production	7/547	34/18670	4.8e-05	7.3e-04	6.0e-04
GO:0050707	regulation of cytokine secretion	18/547	210/18670	4.9e-05	7.4e-04	6.1e-04
GO:0032945	negative regulation of mononuclear cell proliferation	10/547	73/18670	5.1e-05	7.6e-04	6.2e-04
GO:0050672	negative regulation of lymphocyte proliferation	10/547	73/18670	5.1e-05	7.6e-04	6.2e-04
GO:0002698	negative regulation of immune effector process	13/547	120/18670	5.1e-05	7.6e-04	6.2e-04
GO:0002407	dendritic cell chemotaxis	6/547	24/18670	5.3e-05	7.8e-04	6.4e-04
GO:0002861	regulation of inflammatory response to antigenic stimulus	6/547	24/18670	5.3e-05	7.8e-04	6.4e-04
GO:2000107	negative regulation of leukocyte apoptotic process	8/547	47/18670	5.9e-05	8.7e-04	7.2e-04
GO:0097553	calcium ion transmembrane import into cytosol	14/547	140/18670	6.4e-05	9.4e-04	7.8e-04
GO:0070374	positive regulation of ERK1 and ERK2 cascade	18/547	215/18670	6.7e-05	9.7e-04	8.0e-04
GO:0002507	tolerance induction	6/547	25/18670	6.8e-05	9.8e-04	8.1e-04
GO:0002719	negative regulation of cytokine production involved in immune response	6/547	25/18670	6.8e-05	9.8e-04	8.1e-04
GO:0032695	negative regulation of interleukin-12 production	5/547	16/18670	7.1e-05	1.0e-03	8.4e-04
GO:0050920	regulation of chemotaxis	18/547	217/18670	7.5e-05	1.1e-03	8.9e-04
GO:0045453	bone resorption	9/547	62/18670	7.6e-05	1.1e-03	9.0e-04
GO:1904894	positive regulation of STAT cascade	11/547	92/18670	7.8e-05	1.1e-03	9.2e-04
GO:0043029	T cell homeostasis	7/547	37/18670	8.6e-05	1.2e-03	1.0e-03
GO:0045730	respiratory burst	7/547	37/18670	8.6e-05	1.2e-03	1.0e-03
GO:0001916	positive regulation of T cell mediated cytotoxicity	6/547	26/18670	8.6e-05	1.2e-03	1.0e-03
GO:0070664	negative regulation of leukocyte proliferation	10/547	78/18670	9.0e-05	1.3e-03	1.0e-03
GO:0006909	phagocytosis	25/547	369/18670	9.7e-05	1.4e-03	1.1e-03
GO:0048535	lymph node development	5/547	17/18670	9.8e-05	1.4e-03	1.1e-03
GO:1904892	regulation of STAT cascade	14/547	146/18670	1.0e-04	1.4e-03	1.2e-03
GO:0002707	negative regulation of lymphocyte mediated immunity	7/547	38/18670	1.0e-04	1.4e-03	1.2e-03
GO:0032620	interleukin-17 production	7/547	38/18670	1.0e-04	1.4e-03	1.2e-03
GO:0002702	positive regulation of production of molecular mediator of immune response	11/547	95/18670	1.0e-04	1.4e-03	1.2e-03
GO:0036336	dendritic cell migration	6/547	27/18670	1.1e-04	1.5e-03	1.2e-03
GO:0097696	STAT cascade	15/547	166/18670	1.1e-04	1.6e-03	1.3e-03
GO:0050856	regulation of T cell receptor signaling pathway	7/547	39/18670	1.2e-04	1.7e-03	1.4e-03
GO:0032653	regulation of interleukin-10 production	8/547	52/18670	1.2e-04	1.7e-03	1.4e-03
GO:0043011	myeloid dendritic cell differentiation	5/547	18/18670	1.3e-04	1.8e-03	1.5e-03
GO:0001768	establishment of T cell polarity	4/547	10/18670	1.3e-04	1.8e-03	1.5e-03
GO:0010818	T cell chemotaxis	6/547	28/18670	1.3e-04	1.8e-03	1.5e-03
GO:0006323	DNA packaging	17/547	210/18670	1.6e-04	2.1e-03	1.8e-03
GO:0030890	positive regulation of B cell proliferation	7/547	41/18670	1.7e-04	2.3e-03	1.9e-03
GO:0002710	negative regulation of T cell mediated immunity	5/547	19/18670	1.8e-04	2.3e-03	1.9e-03
GO:0000018	regulation of DNA recombination	11/547	101/18670	1.8e-04	2.4e-03	2.0e-03
GO:0032613	interleukin-10 production	8/547	55/18670	1.9e-04	2.5e-03	2.0e-03
GO:0018108	peptidyl-tyrosine phosphorylation	24/547	363/18670	1.9e-04	2.5e-03	2.1e-03
GO:0002639	positive regulation of immunoglobulin production	7/547	42/18670	2.0e-04	2.6e-03	2.1e-03
GO:0050766	positive regulation of phagocytosis	9/547	70/18670	2.0e-04	2.6e-03	2.1e-03
GO:0046425	regulation of JAK-STAT cascade	13/547	137/18670	2.0e-04	2.6e-03	2.1e-03
GO:0002367	cytokine production involved in immune response	11/547	102/18670	2.0e-04	2.6e-03	2.1e-03
GO:0046640	regulation of alpha-beta T cell proliferation	6/547	30/18670	2.0e-04	2.6e-03	2.1e-03
GO:0001767	establishment of lymphocyte polarity	4/547	11/18670	2.0e-04	2.6e-03	2.2e-03
GO:0002517	T cell tolerance induction	4/547	11/18670	2.0e-04	2.6e-03	2.2e-03
GO:0007259	JAK-STAT cascade	14/547	156/18670	2.1e-04	2.6e-03	2.2e-03
GO:0007260	tyrosine phosphorylation of STAT protein	10/547	86/18670	2.1e-04	2.7e-03	2.2e-03
GO:0018212	peptidyl-tyrosine modification	24/547	366/18670	2.2e-04	2.8e-03	2.3e-03
GO:0051897	positive regulation of protein kinase B signaling	15/547	176/18670	2.2e-04	2.8e-03	2.3e-03
GO:0002577	regulation of antigen processing and presentation	5/547	20/18670	2.3e-04	2.9e-03	2.4e-03
GO:0002675	positive regulation of acute inflammatory response	6/547	31/18670	2.4e-04	3.1e-03	2.5e-03
GO:0051482	positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	6/547	31/18670	2.4e-04	3.1e-03	2.5e-03
GO:2000406	positive regulation of T cell migration	6/547	31/18670	2.4e-04	3.1e-03	2.5e-03
GO:1903557	positive regulation of tumor necrosis factor superfamily cytokine production	10/547	88/18670	2.5e-04	3.1e-03	2.6e-03
GO:0034341	response to interferon-gamma	16/547	199/18670	2.6e-04	3.3e-03	2.7e-03
GO:0046427	positive regulation of JAK-STAT cascade	10/547	89/18670	2.7e-04	3.4e-03	2.8e-03
GO:0071103	DNA conformation change	22/547	327/18670	2.7e-04	3.4e-03	2.8e-03
GO:0071346	cellular response to interferon-gamma	15/547	180/18670	2.8e-04	3.5e-03	2.8e-03
GO:0071353	cellular response to interleukin-4	6/547	32/18670	2.9e-04	3.6e-03	3.0e-03
GO:0035590	purinergic nucleotide receptor signaling pathway	5/547	21/18670	2.9e-04	3.6e-03	3.0e-03
GO:0045579	positive regulation of B cell differentiation	4/547	12/18670	3.0e-04	3.7e-03	3.0e-03
GO:0048302	regulation of isotype switching to IgG isotypes	4/547	12/18670	3.0e-04	3.7e-03	3.0e-03
GO:0045581	negative regulation of T cell differentiation	7/547	45/18670	3.1e-04	3.8e-03	3.1e-03
GO:0002573	myeloid leukocyte differentiation	16/547	204/18670	3.5e-04	4.3e-03	3.5e-03
GO:0033622	integrin activation	5/547	22/18670	3.7e-04	4.5e-03	3.7e-03
GO:0072643	interferon-gamma secretion	5/547	22/18670	3.7e-04	4.5e-03	3.7e-03
GO:2001251	negative regulation of chromosome organization	13/547	146/18670	3.7e-04	4.5e-03	3.7e-03
GO:0031334	positive regulation of protein complex assembly	19/547	268/18670	3.7e-04	4.5e-03	3.7e-03
GO:0019882	antigen processing and presentation	17/547	226/18670	3.8e-04	4.5e-03	3.7e-03
GO:0043547	positive regulation of GTPase activity	25/547	405/18670	4.0e-04	4.8e-03	4.0e-03
GO:0030261	chromosome condensation	7/547	47/18670	4.1e-04	4.8e-03	4.0e-03
GO:0070670	response to interleukin-4	6/547	34/18670	4.1e-04	4.9e-03	4.0e-03
GO:0033623	regulation of integrin activation	4/547	13/18670	4.2e-04	5.0e-03	4.1e-03
GO:0048291	isotype switching to IgG isotypes	4/547	13/18670	4.2e-04	5.0e-03	4.1e-03
GO:1902713	regulation of interferon-gamma secretion	4/547	13/18670	4.2e-04	5.0e-03	4.1e-03
GO:0043087	regulation of GTPase activity	28/547	479/18670	4.4e-04	5.2e-03	4.3e-03
GO:0001774	microglial cell activation	7/547	48/18670	4.6e-04	5.4e-03	4.5e-03
GO:0002269	leukocyte activation involved in inflammatory response	7/547	48/18670	4.6e-04	5.4e-03	4.5e-03
GO:0032735	positive regulation of interleukin-12 production	6/547	35/18670	4.8e-04	5.7e-03	4.7e-03
GO:0002534	cytokine production involved in inflammatory response	7/547	49/18670	5.3e-04	6.1e-03	5.0e-03
GO:0045670	regulation of osteoclast differentiation	8/547	64/18670	5.4e-04	6.2e-03	5.1e-03
GO:0046579	positive regulation of Ras protein signal transduction	8/547	64/18670	5.4e-04	6.2e-03	5.1e-03
GO:0042832	defense response to protozoan	5/547	24/18670	5.7e-04	6.5e-03	5.4e-03
GO:0046639	negative regulation of alpha-beta T cell differentiation	5/547	24/18670	5.7e-04	6.5e-03	5.4e-03
GO:0090023	positive regulation of neutrophil chemotaxis	5/547	24/18670	5.7e-04	6.5e-03	5.4e-03
GO:0001771	immunological synapse formation	4/547	14/18670	5.8e-04	6.6e-03	5.4e-03
GO:0050848	regulation of calcium-mediated signaling	10/547	98/18670	6.0e-04	6.8e-03	5.6e-03
GO:2000403	positive regulation of lymphocyte migration	6/547	37/18670	6.6e-04	7.5e-03	6.2e-03
GO:0009615	response to virus	21/547	326/18670	6.6e-04	7.5e-03	6.2e-03
GO:0001562	response to protozoan	5/547	25/18670	6.9e-04	7.8e-03	6.4e-03
GO:0042509	regulation of tyrosine phosphorylation of STAT protein	9/547	83/18670	7.1e-04	8.0e-03	6.6e-03
GO:0051260	protein homooligomerization	22/547	351/18670	7.2e-04	8.1e-03	6.6e-03
GO:0032611	interleukin-1 beta production	10/547	101/18670	7.6e-04	8.5e-03	7.0e-03
GO:0046636	negative regulation of alpha-beta T cell activation	6/547	38/18670	7.6e-04	8.6e-03	7.0e-03
GO:0050715	positive regulation of cytokine secretion	12/547	139/18670	8.1e-04	9.0e-03	7.4e-03
GO:0071624	positive regulation of granulocyte chemotaxis	5/547	26/18670	8.4e-04	9.3e-03	7.7e-03
GO:0032715	negative regulation of interleukin-6 production	7/547	53/18670	8.5e-04	9.4e-03	7.8e-03
GO:0050702	interleukin-1 beta secretion	7/547	53/18670	8.5e-04	9.4e-03	7.8e-03
GO:0070228	regulation of lymphocyte apoptotic process	7/547	53/18670	8.5e-04	9.4e-03	7.8e-03
GO:0046330	positive regulation of JNK cascade	12/547	140/18670	8.6e-04	9.5e-03	7.8e-03
GO:0007229	integrin-mediated signaling pathway	10/547	103/18670	8.8e-04	9.7e-03	7.9e-03
GO:1902106	negative regulation of leukocyte differentiation	10/547	103/18670	8.8e-04	9.7e-03	7.9e-03
GO:0070227	lymphocyte apoptotic process	8/547	69/18670	9.0e-04	9.8e-03	8.1e-03
GO:0032760	positive regulation of tumor necrosis factor production	9/547	86/18670	9.2e-04	1.0e-02	8.3e-03
GO:0032720	negative regulation of tumor necrosis factor production	8/547	70/18670	9.9e-04	1.1e-02	8.8e-03
GO:0034121	regulation of toll-like receptor signaling pathway	8/547	70/18670	9.9e-04	1.1e-02	8.8e-03
GO:0002475	antigen processing and presentation via MHC class Ib	4/547	16/18670	1.0e-03	1.1e-02	8.8e-03
GO:0030889	negative regulation of B cell proliferation	4/547	16/18670	1.0e-03	1.1e-02	8.8e-03
GO:0033631	cell-cell adhesion mediated by integrin	4/547	16/18670	1.0e-03	1.1e-02	8.8e-03
GO:0002825	regulation of T-helper 1 type immune response	5/547	27/18670	1.0e-03	1.1e-02	8.8e-03
GO:1901623	regulation of lymphocyte chemotaxis	5/547	27/18670	1.0e-03	1.1e-02	8.8e-03
GO:0042036	negative regulation of cytokine biosynthetic process	6/547	40/18670	1.0e-03	1.1e-02	8.9e-03
GO:0007249	I-kappaB kinase/NF-kappaB signaling	18/547	269/18670	1.0e-03	1.1e-02	8.9e-03
GO:0051056	regulation of small GTPase mediated signal transduction	21/547	338/18670	1.0e-03	1.1e-02	9.2e-03
GO:0045620	negative regulation of lymphocyte differentiation	7/547	55/18670	1.1e-03	1.1e-02	9.3e-03
GO:0042531	positive regulation of tyrosine phosphorylation of STAT protein	8/547	71/18670	1.1e-03	1.1e-02	9.4e-03
GO:0051057	positive regulation of small GTPase mediated signal transduction	8/547	71/18670	1.1e-03	1.1e-02	9.4e-03
GO:0007088	regulation of mitotic nuclear division	13/547	164/18670	1.1e-03	1.2e-02	9.6e-03
GO:0051321	meiotic cell cycle	17/547	249/18670	1.1e-03	1.2e-02	9.7e-03
GO:0007520	myoblast fusion	6/547	41/18670	1.2e-03	1.2e-02	9.9e-03
GO:0150077	regulation of neuroinflammatory response	6/547	41/18670	1.2e-03	1.2e-02	9.9e-03
GO:0006334	nucleosome assembly	12/547	145/18670	1.2e-03	1.2e-02	1.0e-02
GO:1903556	negative regulation of tumor necrosis factor superfamily cytokine production	8/547	72/18670	1.2e-03	1.2e-02	1.0e-02
GO:0000768	syncytium formation by plasma membrane fusion	7/547	56/18670	1.2e-03	1.2e-02	1.0e-02
GO:0140253	cell-cell fusion	7/547	56/18670	1.2e-03	1.2e-02	1.0e-02
GO:0007076	mitotic chromosome condensation	4/547	17/18670	1.3e-03	1.3e-02	1.1e-02
GO:0010819	regulation of T cell chemotaxis	4/547	17/18670	1.3e-03	1.3e-02	1.1e-02
GO:0032740	positive regulation of interleukin-17 production	4/547	17/18670	1.3e-03	1.3e-02	1.1e-02
GO:0045072	regulation of interferon-gamma biosynthetic process	4/547	17/18670	1.3e-03	1.3e-02	1.1e-02
GO:0045132	meiotic chromosome segregation	9/547	90/18670	1.3e-03	1.3e-02	1.1e-02
GO:0046849	bone remodeling	9/547	90/18670	1.3e-03	1.3e-02	1.1e-02
GO:1903046	meiotic cell cycle process	14/547	188/18670	1.3e-03	1.3e-02	1.1e-02
GO:0035025	positive regulation of Rho protein signal transduction	5/547	29/18670	1.4e-03	1.4e-02	1.2e-02
GO:0060142	regulation of syncytium formation by plasma membrane fusion	5/547	29/18670	1.4e-03	1.4e-02	1.2e-02
GO:1902624	positive regulation of neutrophil migration	5/547	29/18670	1.4e-03	1.4e-02	1.2e-02
GO:0043254	regulation of protein complex assembly	26/547	467/18670	1.4e-03	1.4e-02	1.2e-02
GO:0070372	regulation of ERK1 and ERK2 cascade	19/547	300/18670	1.4e-03	1.4e-02	1.2e-02
GO:0006949	syncytium formation	7/547	58/18670	1.5e-03	1.5e-02	1.2e-02
GO:0061900	glial cell activation	7/547	58/18670	1.5e-03	1.5e-02	1.2e-02
GO:0042088	T-helper 1 type immune response	6/547	43/18670	1.5e-03	1.5e-02	1.2e-02
GO:0050850	positive regulation of calcium-mediated signaling	6/547	43/18670	1.5e-03	1.5e-02	1.2e-02
GO:0150076	neuroinflammatory response	8/547	75/18670	1.6e-03	1.5e-02	1.3e-02
GO:0042095	interferon-gamma biosynthetic process	4/547	18/18670	1.6e-03	1.6e-02	1.3e-02
GO:0051023	regulation of immunoglobulin secretion	4/547	18/18670	1.6e-03	1.6e-02	1.3e-02
GO:0051782	negative regulation of cell division	4/547	18/18670	1.6e-03	1.6e-02	1.3e-02
GO:0042130	negative regulation of T cell proliferation	7/547	59/18670	1.6e-03	1.6e-02	1.3e-02
GO:0001782	B cell homeostasis	5/547	30/18670	1.6e-03	1.6e-02	1.3e-02
GO:0050690	regulation of defense response to virus by virus	5/547	30/18670	1.6e-03	1.6e-02	1.3e-02
GO:0090022	regulation of neutrophil chemotaxis	5/547	30/18670	1.6e-03	1.6e-02	1.3e-02
GO:0045910	negative regulation of DNA recombination	6/547	44/18670	1.7e-03	1.6e-02	1.3e-02
GO:0032874	positive regulation of stress-activated MAPK cascade	13/547	172/18670	1.7e-03	1.6e-02	1.4e-02
GO:0140013	meiotic nuclear division	13/547	172/18670	1.7e-03	1.6e-02	1.4e-02
GO:0043122	regulation of I-kappaB kinase/NF-kappaB signaling	16/547	237/18670	1.7e-03	1.7e-02	1.4e-02
GO:0070304	positive regulation of stress-activated protein kinase signaling cascade	13/547	173/18670	1.8e-03	1.7e-02	1.4e-02
GO:0045576	mast cell activation	7/547	60/18670	1.8e-03	1.7e-02	1.4e-02
GO:0042116	macrophage activation	9/547	95/18670	1.9e-03	1.8e-02	1.5e-02
GO:0002724	regulation of T cell cytokine production	5/547	31/18670	1.9e-03	1.8e-02	1.5e-02
GO:0007202	activation of phospholipase C activity	5/547	31/18670	1.9e-03	1.8e-02	1.5e-02
GO:0002920	regulation of humoral immune response	11/547	134/18670	2.0e-03	1.9e-02	1.5e-02
GO:0050701	interleukin-1 secretion	7/547	61/18670	2.0e-03	1.9e-02	1.5e-02
GO:0002544	chronic inflammatory response	4/547	19/18670	2.0e-03	1.9e-02	1.5e-02
GO:0060252	positive regulation of glial cell proliferation	4/547	19/18670	2.0e-03	1.9e-02	1.5e-02
GO:0071800	podosome assembly	4/547	19/18670	2.0e-03	1.9e-02	1.5e-02
GO:0032612	interleukin-1 production	10/547	115/18670	2.0e-03	1.9e-02	1.6e-02
GO:1903707	negative regulation of hemopoiesis	12/547	155/18670	2.1e-03	1.9e-02	1.6e-02
GO:1900015	regulation of cytokine production involved in inflammatory response	6/547	46/18670	2.1e-03	2.0e-02	1.6e-02
GO:0035587	purinergic receptor signaling pathway	5/547	32/18670	2.2e-03	2.1e-02	1.7e-02
GO:0050764	regulation of phagocytosis	9/547	98/18670	2.3e-03	2.2e-02	1.8e-02
GO:0033045	regulation of sister chromatid segregation	8/547	80/18670	2.4e-03	2.2e-02	1.8e-02
GO:0033630	positive regulation of cell adhesion mediated by integrin	4/547	20/18670	2.4e-03	2.2e-02	1.8e-02
GO:0042535	positive regulation of tumor necrosis factor biosynthetic process	4/547	20/18670	2.4e-03	2.2e-02	1.8e-02
GO:0043371	negative regulation of CD4-positive, alpha-beta T cell differentiation	4/547	20/18670	2.4e-03	2.2e-02	1.8e-02
GO:1900017	positive regulation of cytokine production involved in inflammatory response	4/547	20/18670	2.4e-03	2.2e-02	1.8e-02
GO:1903978	regulation of microglial cell activation	4/547	20/18670	2.4e-03	2.2e-02	1.8e-02
GO:0070588	calcium ion transmembrane transport	19/547	315/18670	2.5e-03	2.3e-02	1.9e-02
GO:0002291	T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	3/547	10/18670	2.6e-03	2.3e-02	1.9e-02
GO:0048304	positive regulation of isotype switching to IgG isotypes	3/547	10/18670	2.6e-03	2.3e-02	1.9e-02
GO:0072610	interleukin-12 secretion	3/547	10/18670	2.6e-03	2.3e-02	1.9e-02
GO:0097048	dendritic cell apoptotic process	3/547	10/18670	2.6e-03	2.3e-02	1.9e-02
GO:2000668	regulation of dendritic cell apoptotic process	3/547	10/18670	2.6e-03	2.3e-02	1.9e-02
GO:0070371	ERK1 and ERK2 cascade	19/547	317/18670	2.7e-03	2.4e-02	2.0e-02
GO:0033044	regulation of chromosome organization	20/547	342/18670	2.8e-03	2.5e-02	2.1e-02
GO:0019884	antigen processing and presentation of exogenous antigen	13/547	182/18670	2.8e-03	2.5e-02	2.1e-02
GO:0030099	myeloid cell differentiation	23/547	416/18670	2.8e-03	2.5e-02	2.1e-02
GO:0042533	tumor necrosis factor biosynthetic process	5/547	34/18670	2.9e-03	2.6e-02	2.1e-02
GO:0042534	regulation of tumor necrosis factor biosynthetic process	5/547	34/18670	2.9e-03	2.6e-02	2.1e-02
GO:0051383	kinetochore organization	4/547	21/18670	2.9e-03	2.6e-02	2.1e-02
GO:1901739	regulation of myoblast fusion	4/547	21/18670	2.9e-03	2.6e-02	2.1e-02
GO:0001894	tissue homeostasis	15/547	227/18670	2.9e-03	2.6e-02	2.1e-02
GO:0002686	negative regulation of leukocyte migration	6/547	49/18670	3.0e-03	2.6e-02	2.1e-02
GO:0046718	viral entry into host cell	10/547	121/18670	3.0e-03	2.6e-02	2.2e-02
GO:0046328	regulation of JNK cascade	13/547	185/18670	3.2e-03	2.8e-02	2.3e-02
GO:0051983	regulation of chromosome segregation	9/547	103/18670	3.3e-03	2.9e-02	2.4e-02
GO:0042092	type 2 immune response	5/547	35/18670	3.3e-03	2.9e-02	2.4e-02
GO:0060251	regulation of glial cell proliferation	5/547	35/18670	3.3e-03	2.9e-02	2.4e-02
GO:0002638	negative regulation of immunoglobulin production	3/547	11/18670	3.5e-03	3.0e-02	2.5e-02
GO:0033632	regulation of cell-cell adhesion mediated by integrin	3/547	11/18670	3.5e-03	3.0e-02	2.5e-02
GO:0071803	positive regulation of podosome assembly	3/547	11/18670	3.5e-03	3.0e-02	2.5e-02
GO:0031497	chromatin assembly	12/547	165/18670	3.5e-03	3.0e-02	2.5e-02
GO:0019883	antigen processing and presentation of endogenous antigen	4/547	22/18670	3.5e-03	3.0e-02	2.5e-02
GO:0045624	positive regulation of T-helper cell differentiation	4/547	22/18670	3.5e-03	3.0e-02	2.5e-02
GO:0002791	regulation of peptide secretion	26/547	500/18670	3.6e-03	3.1e-02	2.5e-02
GO:0030071	regulation of mitotic metaphase/anaphase transition	6/547	51/18670	3.6e-03	3.1e-02	2.6e-02
GO:0033627	cell adhesion mediated by integrin	7/547	68/18670	3.7e-03	3.2e-02	2.6e-02
GO:0051783	regulation of nuclear division	13/547	188/18670	3.7e-03	3.2e-02	2.6e-02
GO:0032733	positive regulation of interleukin-10 production	5/547	36/18670	3.8e-03	3.2e-02	2.6e-02
GO:1902622	regulation of neutrophil migration	5/547	36/18670	3.8e-03	3.2e-02	2.6e-02
GO:0002224	toll-like receptor signaling pathway	11/547	146/18670	3.9e-03	3.3e-02	2.7e-02
GO:0032703	negative regulation of interleukin-2 production	4/547	23/18670	4.1e-03	3.5e-02	2.9e-02
GO:0038083	peptidyl-tyrosine autophosphorylation	5/547	37/18670	4.3e-03	3.6e-02	3.0e-02
GO:0007254	JNK cascade	14/547	214/18670	4.4e-03	3.7e-02	3.0e-02
GO:0032872	regulation of stress-activated MAPK cascade	15/547	237/18670	4.4e-03	3.7e-02	3.0e-02
GO:0045840	positive regulation of mitotic nuclear division	6/547	53/18670	4.4e-03	3.7e-02	3.0e-02
GO:1902099	regulation of metaphase/anaphase transition of cell cycle	6/547	53/18670	4.4e-03	3.7e-02	3.0e-02
GO:0038110	interleukin-2-mediated signaling pathway	3/547	12/18670	4.5e-03	3.7e-02	3.1e-02
GO:0042368	vitamin D biosynthetic process	3/547	12/18670	4.5e-03	3.7e-02	3.1e-02
GO:0046541	saliva secretion	3/547	12/18670	4.5e-03	3.7e-02	3.1e-02
GO:0048934	peripheral nervous system neuron differentiation	3/547	12/18670	4.5e-03	3.7e-02	3.1e-02
GO:0048935	peripheral nervous system neuron development	3/547	12/18670	4.5e-03	3.7e-02	3.1e-02
GO:0070601	centromeric sister chromatid cohesion	3/547	12/18670	4.5e-03	3.7e-02	3.1e-02
GO:0070302	regulation of stress-activated protein kinase signaling cascade	15/547	239/18670	4.7e-03	3.9e-02	3.2e-02
GO:0007091	metaphase/anaphase transition of mitotic cell cycle	6/547	54/18670	4.8e-03	4.0e-02	3.3e-02
GO:0010524	positive regulation of calcium ion transport into cytosol	6/547	54/18670	4.8e-03	4.0e-02	3.3e-02
GO:0032651	regulation of interleukin-1 beta production	8/547	90/18670	4.9e-03	4.0e-02	3.3e-02
GO:0051304	chromosome separation	8/547	90/18670	4.9e-03	4.0e-02	3.3e-02
GO:0002793	positive regulation of peptide secretion	17/547	288/18670	5.1e-03	4.2e-02	3.4e-02
GO:0043030	regulation of macrophage activation	6/547	55/18670	5.3e-03	4.3e-02	3.5e-02
GO:0043551	regulation of phosphatidylinositol 3-kinase activity	6/547	55/18670	5.3e-03	4.3e-02	3.5e-02
GO:0061844	antimicrobial humoral immune response mediated by antimicrobial peptide	7/547	73/18670	5.5e-03	4.5e-02	3.7e-02
GO:0045807	positive regulation of endocytosis	11/547	153/18670	5.5e-03	4.5e-02	3.7e-02
GO:0032461	positive regulation of protein oligomerization	4/547	25/18670	5.7e-03	4.6e-02	3.8e-02
GO:0045672	positive regulation of osteoclast differentiation	4/547	25/18670	5.7e-03	4.6e-02	3.8e-02
GO:2000482	regulation of interleukin-8 secretion	4/547	25/18670	5.7e-03	4.6e-02	3.8e-02
GO:0051896	regulation of protein kinase B signaling	15/547	244/18670	5.7e-03	4.6e-02	3.8e-02
GO:0030656	regulation of vitamin metabolic process	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:0035723	interleukin-15-mediated signaling pathway	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:0042635	positive regulation of hair cycle	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:0045779	negative regulation of bone resorption	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:0071350	cellular response to interleukin-15	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:0071352	cellular response to interleukin-2	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:1900225	regulation of NLRP3 inflammasome complex assembly	3/547	13/18670	5.7e-03	4.6e-02	3.8e-02
GO:0044784	metaphase/anaphase transition of cell cycle	6/547	56/18670	5.8e-03	4.6e-02	3.8e-02
GO:0014015	positive regulation of gliogenesis	7/547	74/18670	5.9e-03	4.7e-02	3.8e-02
GO:0050710	negative regulation of cytokine secretion	7/547	74/18670	5.9e-03	4.7e-02	3.8e-02
GO:0002369	T cell cytokine production	5/547	40/18670	6.0e-03	4.7e-02	3.9e-02
GO:0045124	regulation of bone resorption	5/547	40/18670	6.0e-03	4.7e-02	3.9e-02
GO:0098760	response to interleukin-7	5/547	40/18670	6.0e-03	4.7e-02	3.9e-02
GO:0098761	cellular response to interleukin-7	5/547	40/18670	6.0e-03	4.7e-02	3.9e-02
GO:0043491	protein kinase B signaling	16/547	269/18670	6.0e-03	4.7e-02	3.9e-02
GO:0030260	entry into host cell	10/547	134/18670	6.1e-03	4.8e-02	3.9e-02
GO:0044409	entry into host	10/547	134/18670	6.1e-03	4.8e-02	3.9e-02
GO:0051806	entry into cell of other organism involved in symbiotic interaction	10/547	134/18670	6.1e-03	4.8e-02	3.9e-02
GO:0051828	entry into other organism involved in symbiotic interaction	10/547	134/18670	6.1e-03	4.8e-02	3.9e-02
GO:0030198	extracellular matrix organization	20/547	368/18670	6.2e-03	4.8e-02	4.0e-02
GO:0010965	regulation of mitotic sister chromatid separation	6/547	57/18670	6.3e-03	4.9e-02	4.0e-02
GO:0002218	activation of innate immune response	18/547	319/18670	6.3e-03	4.9e-02	4.0e-02

Tabla 11: GOtable que contiene las vías metabólicas expresadas diferencialmente entre los grupos NIT y ELI.

SFI vs ELI:

	Description	GeneRatio	BgRatio	pvalue	p.adjust	qvalue
GO:0042110	T cell activation	61/409	464/18670	4.5e-30	1.7e-26	1.5e-26
GO:0051249	regulation of lymphocyte activation	57/409	485/18670	1.4e-25	2.6e-22	2.2e-22
GO:0050863	regulation of T cell activation	46/409	314/18670	8.0e-25	1.0e-21	8.7e-22
GO:0030098	lymphocyte differentiation	48/409	353/18670	2.1e-24	2.0e-21	1.7e-21
GO:0022409	positive regulation of cell-cell adhesion	38/409	255/18670	6.4e-21	4.3e-18	3.7e-18
GO:0007159	leukocyte cell-cell adhesion	43/409	337/18670	7.4e-21	4.3e-18	3.7e-18
GO:0046651	lymphocyte proliferation	39/409	272/18670	7.8e-21	4.3e-18	3.7e-18
GO:0032943	mononuclear cell proliferation	39/409	274/18670	1.0e-20	4.9e-18	4.2e-18
GO:0050870	positive regulation of T cell activation	34/409	202/18670	1.5e-20	6.3e-18	5.3e-18
GO:1903039	positive regulation of leukocyte cell-cell adhesion	35/409	218/18670	2.0e-20	7.5e-18	6.4e-18
GO:0070661	leukocyte proliferation	40/409	298/18670	2.8e-20	9.9e-18	8.4e-18
GO:1903037	regulation of leukocyte cell-cell adhesion	40/409	304/18670	5.9e-20	1.9e-17	1.6e-17
GO:0030217	T cell differentiation	34/409	240/18670	4.0e-18	1.2e-15	9.9e-16
GO:0002696	positive regulation of leukocyte activation	42/409	380/18670	4.9e-18	1.3e-15	1.1e-15
GO:0022407	regulation of cell-cell adhesion	43/409	403/18670	7.2e-18	1.8e-15	1.6e-15
GO:0051251	positive regulation of lymphocyte activation	39/409	334/18670	1.2e-17	2.9e-15	2.5e-15
GO:0050867	positive regulation of cell activation	42/409	394/18670	1.8e-17	4.1e-15	3.5e-15
GO:0050670	regulation of lymphocyte proliferation	31/409	208/18670	2.9e-17	6.1e-15	5.2e-15
GO:0032944	regulation of mononuclear cell proliferation	31/409	209/18670	3.3e-17	6.6e-15	5.6e-15
GO:0070663	regulation of leukocyte proliferation	31/409	222/18670	1.9e-16	3.6e-14	3.1e-14
GO:0042113	B cell activation	35/409	310/18670	1.7e-15	3.1e-13	2.7e-13
GO:0045785	positive regulation of cell adhesion	38/409	403/18670	3.6e-14	6.3e-12	5.4e-12
GO:0042129	regulation of T cell proliferation	24/409	156/18670	5.8e-14	9.7e-12	8.2e-12
GO:0046631	alpha-beta T cell activation	22/409	138/18670	3.1e-13	4.8e-11	4.1e-11
GO:0042098	T cell proliferation	25/409	184/18670	3.2e-13	4.8e-11	4.1e-11
GO:0050851	antigen receptor-mediated signaling pathway	32/409	316/18670	6.0e-13	8.8e-11	7.5e-11
GO:0002460	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	34/409	361/18670	8.9e-13	1.3e-10	1.1e-10
GO:0042100	B cell proliferation	18/409	95/18670	2.2e-12	2.8e-10	2.4e-10
GO:0042102	positive regulation of T cell proliferation	18/409	95/18670	2.2e-12	2.8e-10	2.4e-10
GO:0002449	lymphocyte mediated immunity	33/409	352/18670	2.2e-12	2.8e-10	2.4e-10
GO:0002429	immune response-activating cell surface receptor signaling pathway	38/409	473/18670	5.2e-12	6.5e-10	5.5e-10
GO:0050671	positive regulation of lymphocyte proliferation	20/409	130/18670	7.5e-12	9.0e-10	7.6e-10
GO:0032946	positive regulation of mononuclear cell proliferation	20/409	131/18670	8.7e-12	1.0e-09	8.6e-10
GO:0070665	positive regulation of leukocyte proliferation	20/409	139/18670	2.7e-11	3.0e-09	2.5e-09
GO:0046632	alpha-beta T cell differentiation	17/409	101/18670	6.6e-11	7.2e-09	6.1e-09
GO:0002285	lymphocyte activation involved in immune response	22/409	181/18670	8.0e-11	8.5e-09	7.2e-09
GO:0043368	positive T cell selection	11/409	34/18670	8.9e-11	9.2e-09	7.8e-09
GO:0045619	regulation of lymphocyte differentiation	21/409	169/18670	1.4e-10	1.4e-08	1.2e-08
GO:0031295	T cell costimulation	13/409	56/18670	1.8e-10	1.7e-08	1.5e-08
GO:0031294	lymphocyte costimulation	13/409	57/18670	2.3e-10	2.2e-08	1.8e-08
GO:0045058	T cell selection	12/409	47/18670	2.7e-10	2.5e-08	2.2e-08
GO:1902105	regulation of leukocyte differentiation	26/409	272/18670	3.4e-10	3.1e-08	2.6e-08
GO:0007059	chromosome segregation	28/409	321/18670	5.8e-10	5.1e-08	4.4e-08
GO:0032729	positive regulation of interferon-gamma production	13/409	65/18670	1.3e-09	1.1e-07	9.6e-08
GO:0002377	immunoglobulin production	21/409	193/18670	1.7e-09	1.4e-07	1.2e-07
GO:0001819	positive regulation of cytokine production	33/409	464/18670	3.2e-09	2.6e-07	2.2e-07
GO:0050853	B cell receptor signaling pathway	17/409	129/18670	3.3e-09	2.7e-07	2.3e-07
GO:0140014	mitotic nuclear division	24/409	264/18670	4.5e-09	3.5e-07	3.0e-07
GO:0002706	regulation of lymphocyte mediated immunity	18/409	149/18670	4.7e-09	3.7e-07	3.1e-07
GO:0050900	leukocyte migration	34/409	499/18670	5.4e-09	4.1e-07	3.5e-07
GO:0045580	regulation of T cell differentiation	17/409	139/18670	1.1e-08	7.9e-07	6.7e-07
GO:0042108	positive regulation of cytokine biosynthetic process	12/409	67/18670	2.1e-08	1.5e-06	1.3e-06
GO:0032609	interferon-gamma production	15/409	113/18670	2.5e-08	1.8e-06	1.6e-06
GO:0000280	nuclear division	29/409	407/18670	2.8e-08	2.0e-06	1.7e-06
GO:0002697	regulation of immune effector process	31/409	458/18670	3.0e-08	2.1e-06	1.8e-06
GO:0000070	mitotic sister chromatid segregation	17/409	151/18670	3.7e-08	2.5e-06	2.1e-06
GO:0000819	sister chromatid segregation	19/409	189/18670	3.7e-08	2.5e-06	2.1e-06
GO:0002683	negative regulation of immune system process	31/409	463/18670	3.9e-08	2.6e-06	2.2e-06
GO:0043367	CD4-positive, alpha-beta T cell differentiation	12/409	74/18670	6.7e-08	4.3e-06	3.7e-06
GO:0002708	positive regulation of lymphocyte mediated immunity	14/409	105/18670	7.0e-08	4.5e-06	3.8e-06
GO:0002819	regulation of adaptive immune response	17/409	160/18670	8.7e-08	5.5e-06	4.6e-06
GO:0046635	positive regulation of alpha-beta T cell activation	11/409	62/18670	9.1e-08	5.6e-06	4.8e-06
GO:0002703	regulation of leukocyte mediated immunity	19/409	201/18670	1.0e-07	6.1e-06	5.2e-06
GO:0030595	leukocyte chemotaxis	20/409	224/18670	1.2e-07	7.1e-06	6.0e-06
GO:0050854	regulation of antigen receptor-mediated signaling pathway	11/409	65/18670	1.5e-07	8.9e-06	7.6e-06
GO:0048285	organelle fission	29/409	449/18670	2.3e-07	1.3e-05	1.1e-05
GO:0002699	positive regulation of immune effector process	19/409	216/18670	3.1e-07	1.8e-05	1.5e-05
GO:0032649	regulation of interferon-gamma production	13/409	101/18670	3.2e-07	1.8e-05	1.5e-05
GO:0033077	T cell differentiation in thymus	11/409	70/18670	3.3e-07	1.8e-05	1.6e-05
GO:0098813	nuclear chromosome segregation	21/409	262/18670	3.5e-07	1.9e-05	1.6e-05
GO:0016064	immunoglobulin mediated immune response	19/409	218/18670	3.6e-07	1.9e-05	1.6e-05
GO:0002440	production of molecular mediator of immune response	22/409	286/18670	3.8e-07	2.0e-05	1.7e-05
GO:0019724	B cell mediated immunity	19/409	221/18670	4.4e-07	2.3e-05	2.0e-05
GO:0002295	T-helper cell lineage commitment	6/409	16/18670	7.1e-07	3.6e-05	3.1e-05
GO:0002822	regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	15/409	145/18670	7.1e-07	3.6e-05	3.1e-05
GO:1903706	regulation of hemopoiesis	29/409	475/18670	7.4e-07	3.7e-05	3.2e-05
GO:0030888	regulation of B cell proliferation	10/409	61/18670	7.6e-07	3.8e-05	3.2e-05
GO:0035710	CD4-positive, alpha-beta T cell activation	12/409	92/18670	7.8e-07	3.8e-05	3.2e-05
GO:0046634	regulation of alpha-beta T cell activation	12/409	93/18670	8.7e-07	4.2e-05	3.6e-05
GO:0043373	CD4-positive, alpha-beta T cell lineage commitment	6/409	17/18670	1.1e-06	5.1e-05	4.4e-05
GO:0030183	B cell differentiation	14/409	131/18670	1.1e-06	5.3e-05	4.5e-05
GO:0006959	humoral immune response	24/409	356/18670	1.2e-06	5.7e-05	4.8e-05
GO:0042035	regulation of cytokine biosynthetic process	13/409	114/18670	1.3e-06	6.0e-05	5.1e-05
GO:0002705	positive regulation of leukocyte mediated immunity	14/409	133/18670	1.3e-06	6.1e-05	5.2e-05
GO:0001773	myeloid dendritic cell activation	7/409	28/18670	1.8e-06	8.2e-05	7.0e-05
GO:0002824	positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	12/409	100/18670	1.9e-06	8.5e-05	7.3e-05
GO:0031343	positive regulation of cell killing	10/409	68/18670	2.1e-06	9.4e-05	8.0e-05
GO:0002363	alpha-beta T cell lineage commitment	6/409	19/18670	2.3e-06	9.9e-05	8.4e-05
GO:0050855	regulation of B cell receptor signaling pathway	7/409	29/18670	2.4e-06	1.0e-04	8.6e-05
GO:0050852	T cell receptor signaling pathway	17/409	202/18670	2.4e-06	1.0e-04	8.6e-05
GO:0001776	leukocyte homeostasis	11/409	86/18670	2.7e-06	1.1e-04	9.8e-05
GO:0042089	cytokine biosynthetic process	13/409	123/18670	3.1e-06	1.3e-04	1.1e-04
GO:0043369	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	6/409	20/18670	3.2e-06	1.3e-04	1.1e-04
GO:0002821	positive regulation of adaptive immune response	12/409	105/18670	3.2e-06	1.3e-04	1.1e-04
GO:0002381	immunoglobulin production involved in immunoglobulin mediated immune response	9/409	56/18670	3.2e-06	1.3e-04	1.1e-04
GO:0042107	cytokine metabolic process	13/409	124/18670	3.4e-06	1.3e-04	1.1e-04
GO:0072540	T-helper 17 cell lineage commitment	5/409	12/18670	3.4e-06	1.4e-04	1.2e-04
GO:1902107	positive regulation of leukocyte differentiation	14/409	144/18670	3.5e-06	1.4e-04	1.2e-04
GO:0002286	T cell activation involved in immune response	12/409	106/18670	3.6e-06	1.4e-04	1.2e-04
GO:0060326	cell chemotaxis	21/409	304/18670	3.9e-06	1.5e-04	1.3e-04
GO:0045061	thymic T cell selection	6/409	21/18670	4.4e-06	1.7e-04	1.4e-04
GO:0045059	positive thymic T cell selection	5/409	13/18670	5.5e-06	2.1e-04	1.7e-04
GO:0048305	immunoglobulin secretion	6/409	22/18670	5.9e-06	2.2e-04	1.9e-04
GO:0045621	positive regulation of lymphocyte differentiation	11/409	94/18670	6.6e-06	2.4e-04	2.1e-04
GO:0002287	alpha-beta T cell activation involved in immune response	9/409	61/18670	6.7e-06	2.4e-04	2.1e-04
GO:0002293	alpha-beta T cell differentiation involved in immune response	9/409	61/18670	6.7e-06	2.4e-04	2.1e-04
GO:0002688	regulation of leukocyte chemotaxis	12/409	114/18670	7.7e-06	2.7e-04	2.3e-04
GO:0007204	positive regulation of cytosolic calcium ion concentration	21/409	319/18670	8.2e-06	2.9e-04	2.5e-04
GO:0031341	regulation of cell killing	11/409	98/18670	9.9e-06	3.5e-04	3.0e-04
GO:0045582	positive regulation of T cell differentiation	10/409	83/18670	1.3e-05	4.6e-04	3.9e-04
GO:0050864	regulation of B cell activation	15/409	184/18670	1.4e-05	4.7e-04	4.0e-04
GO:0007088	regulation of mitotic nuclear division	14/409	164/18670	1.6e-05	5.4e-04	4.6e-04
GO:0002292	T cell differentiation involved in immune response	9/409	68/18670	1.7e-05	5.7e-04	4.8e-04
GO:0002360	T cell lineage commitment	6/409	26/18670	1.7e-05	5.7e-04	4.8e-04
GO:0051783	regulation of nuclear division	15/409	188/18670	1.8e-05	5.9e-04	5.0e-04
GO:0001906	cell killing	14/409	168/18670	2.1e-05	6.8e-04	5.8e-04
GO:0001909	leukocyte mediated cytotoxicity	11/409	107/18670	2.3e-05	7.5e-04	6.4e-04
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	8/409	56/18670	2.8e-05	9.1e-04	7.7e-04
GO:0002685	regulation of leukocyte migration	15/409	196/18670	2.9e-05	9.3e-04	7.9e-04
GO:0002312	B cell activation involved in immune response	9/409	73/18670	3.0e-05	9.5e-04	8.1e-04
GO:1902850	microtubule cytoskeleton organization involved in mitosis	12/409	131/18670	3.2e-05	1.0e-03	8.5e-04
GO:0032103	positive regulation of response to external stimulus	20/409	323/18670	3.2e-05	1.0e-03	8.6e-04
GO:0002695	negative regulation of leukocyte activation	14/409	175/18670	3.3e-05	1.0e-03	8.6e-04
GO:0051480	regulation of cytosolic calcium ion concentration	21/409	357/18670	4.4e-05	1.3e-03	1.1e-03
GO:0046641	positive regulation of alpha-beta T cell proliferation	5/409	19/18670	4.4e-05	1.4e-03	1.2e-03
GO:0002294	CD4-positive, alpha-beta T cell differentiation involved in immune response	8/409	60/18670	4.7e-05	1.4e-03	1.2e-03
GO:0001910	regulation of leukocyte mediated cytotoxicity	9/409	78/18670	5.1e-05	1.5e-03	1.3e-03
GO:0002260	lymphocyte homeostasis	8/409	62/18670	6.0e-05	1.8e-03	1.5e-03
GO:1903708	positive regulation of hemopoiesis	14/409	185/18670	6.0e-05	1.8e-03	1.5e-03
GO:0002923	regulation of humoral immune response mediated by circulating immunoglobulin	4/409	11/18670	6.6e-05	1.9e-03	1.7e-03
GO:0002637	regulation of immunoglobulin production	8/409	63/18670	6.7e-05	1.9e-03	1.7e-03
GO:0046637	regulation of alpha-beta T cell differentiation	8/409	63/18670	6.7e-05	1.9e-03	1.7e-03
GO:0046638	positive regulation of alpha-beta T cell differentiation	7/409	47/18670	6.8e-05	2.0e-03	1.7e-03
GO:0046633	alpha-beta T cell proliferation	6/409	33/18670	7.1e-05	2.0e-03	1.7e-03
GO:0072678	T cell migration	8/409	65/18670	8.4e-05	2.4e-03	2.0e-03
GO:0019722	calcium-mediated signaling	15/409	218/18670	9.8e-05	2.7e-03	2.3e-03
GO:0048872	homeostasis of number of cells	16/409	246/18670	1.1e-04	3.1e-03	2.7e-03
GO:0002687	positive regulation of leukocyte migration	11/409	128/18670	1.2e-04	3.3e-03	2.8e-03
GO:0002690	positive regulation of leukocyte chemotaxis	9/409	87/18670	1.2e-04	3.3e-03	2.8e-03
GO:0055074	calcium ion homeostasis	24/409	471/18670	1.2e-04	3.3e-03	2.8e-03
GO:0050866	negative regulation of cell activation	14/409	199/18670	1.3e-04	3.6e-03	3.0e-03
GO:0050729	positive regulation of inflammatory response	12/409	153/18670	1.4e-04	3.8e-03	3.2e-03
GO:0002709	regulation of T cell mediated immunity	8/409	70/18670	1.4e-04	3.8e-03	3.2e-03
GO:0048469	cell maturation	13/409	177/18670	1.5e-04	3.9e-03	3.3e-03
GO:0042832	defense response to protozoan	5/409	24/18670	1.5e-04	3.9e-03	3.3e-03
GO:0050857	positive regulation of antigen receptor-mediated signaling pathway	5/409	24/18670	1.5e-04	3.9e-03	3.3e-03
GO:0001562	response to protozoan	5/409	25/18670	1.8e-04	4.7e-03	4.0e-03
GO:0021700	developmental maturation	17/409	284/18670	1.9e-04	4.8e-03	4.1e-03
GO:0043374	CD8-positive, alpha-beta T cell differentiation	4/409	14/18670	1.9e-04	4.9e-03	4.2e-03
GO:0006909	phagocytosis	20/409	369/18670	2.0e-04	5.1e-03	4.3e-03
GO:1903532	positive regulation of secretion by cell	21/409	399/18670	2.1e-04	5.2e-03	4.5e-03
GO:0006874	cellular calcium ion homeostasis	23/409	458/18670	2.1e-04	5.2e-03	4.5e-03
GO:0072539	T-helper 17 cell differentiation	5/409	26/18670	2.2e-04	5.5e-03	4.7e-03
GO:0071216	cellular response to biotic stimulus	15/409	236/18670	2.3e-04	5.8e-03	4.9e-03
GO:0071219	cellular response to molecule of bacterial origin	14/409	212/18670	2.5e-04	6.2e-03	5.3e-03
GO:0042093	T-helper cell differentiation	7/409	58/18670	2.6e-04	6.5e-03	5.5e-03
GO:0045577	regulation of B cell differentiation	5/409	28/18670	3.2e-04	7.7e-03	6.6e-03
GO:0045165	cell fate commitment	16/409	270/18670	3.2e-04	7.7e-03	6.6e-03
GO:0033209	tumor necrosis factor-mediated signaling pathway	12/409	167/18670	3.2e-04	7.7e-03	6.6e-03
GO:2000404	regulation of T cell migration	6/409	44/18670	3.7e-04	8.9e-03	7.6e-03
GO:0072538	T-helper 17 type immune response	5/409	29/18670	3.8e-04	8.9e-03	7.6e-03
GO:0051250	negative regulation of lymphocyte activation	11/409	146/18670	3.8e-04	8.9e-03	7.6e-03
GO:0000910	cytokinesis	12/409	171/18670	4.0e-04	9.4e-03	8.0e-03
GO:0051321	meiotic cell cycle	15/409	249/18670	4.1e-04	9.6e-03	8.2e-03
GO:0048535	lymph node development	4/409	17/18670	4.3e-04	1.0e-02	8.5e-03
GO:0051983	regulation of chromosome segregation	9/409	103/18670	4.3e-04	1.0e-02	8.5e-03
GO:0032743	positive regulation of interleukin-2 production	5/409	30/18670	4.5e-04	1.0e-02	8.7e-03
GO:0046640	regulation of alpha-beta T cell proliferation	5/409	30/18670	4.5e-04	1.0e-02	8.7e-03
GO:0071887	leukocyte apoptotic process	9/409	104/18670	4.7e-04	1.1e-02	9.0e-03
GO:0002675	positive regulation of acute inflammatory response	5/409	31/18670	5.2e-04	1.2e-02	1.0e-02
GO:0051482	positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	5/409	31/18670	5.2e-04	1.2e-02	1.0e-02
GO:0051047	positive regulation of secretion	21/409	428/18670	5.3e-04	1.2e-02	1.0e-02
GO:0043370	regulation of CD4-positive, alpha-beta T cell differentiation	6/409	47/18670	5.4e-04	1.2e-02	1.0e-02
GO:0007052	mitotic spindle organization	9/409	106/18670	5.4e-04	1.2e-02	1.0e-02
GO:0043011	myeloid dendritic cell differentiation	4/409	18/18670	5.4e-04	1.2e-02	1.0e-02
GO:0051023	regulation of immunoglobulin secretion	4/409	18/18670	5.4e-04	1.2e-02	1.0e-02
GO:0051782	negative regulation of cell division	4/409	18/18670	5.4e-04	1.2e-02	1.0e-02
GO:0034612	response to tumor necrosis factor	17/409	312/18670	5.6e-04	1.2e-02	1.0e-02
GO:0072503	cellular divalent inorganic cation homeostasis	23/409	493/18670	5.9e-04	1.3e-02	1.1e-02
GO:0051785	positive regulation of nuclear division	7/409	66/18670	5.9e-04	1.3e-02	1.1e-02
GO:0002237	response to molecule of bacterial origin	18/409	343/18670	6.0e-04	1.3e-02	1.1e-02
GO:0071222	cellular response to lipopolysaccharide	13/409	205/18670	6.1e-04	1.3e-02	1.1e-02
GO:0002544	chronic inflammatory response	4/409	19/18670	6.8e-04	1.4e-02	1.2e-02
GO:0060252	positive regulation of glial cell proliferation	4/409	19/18670	6.8e-04	1.4e-02	1.2e-02
GO:0032633	interleukin-4 production	5/409	33/18670	7.0e-04	1.5e-02	1.2e-02
GO:0071356	cellular response to tumor necrosis factor	16/409	291/18670	7.3e-04	1.5e-02	1.3e-02
GO:0072676	lymphocyte migration	9/409	111/18670	7.5e-04	1.5e-02	1.3e-02
GO:0097529	myeloid leukocyte migration	13/409	210/18670	7.7e-04	1.6e-02	1.3e-02
GO:0070227	lymphocyte apoptotic process	7/409	69/18670	7.7e-04	1.6e-02	1.3e-02
GO:0045132	meiotic chromosome segregation	8/409	90/18670	8.0e-04	1.6e-02	1.4e-02
GO:0045066	regulatory T cell differentiation	5/409	34/18670	8.1e-04	1.6e-02	1.4e-02
GO:0002712	regulation of B cell mediated immunity	6/409	51/18670	8.3e-04	1.6e-02	1.4e-02
GO:0002889	regulation of immunoglobulin mediated immune response	6/409	51/18670	8.3e-04	1.6e-02	1.4e-02
GO:0030071	regulation of mitotic metaphase/anaphase transition	6/409	51/18670	8.3e-04	1.6e-02	1.4e-02
GO:0050766	positive regulation of phagocytosis	7/409	70/18670	8.4e-04	1.6e-02	1.4e-02
GO:0060251	regulation of glial cell proliferation	5/409	35/18670	9.3e-04	1.8e-02	1.5e-02
GO:0090068	positive regulation of cell cycle process	16/409	298/18670	9.4e-04	1.8e-02	1.5e-02
GO:0002700	regulation of production of molecular mediator of immune response	10/409	139/18670	9.9e-04	1.9e-02	1.6e-02
GO:0051383	kinetochore organization	4/409	21/18670	1.0e-03	1.9e-02	1.6e-02
GO:0045787	positive regulation of cell cycle	19/409	389/18670	1.0e-03	1.9e-02	1.6e-02
GO:0045840	positive regulation of mitotic nuclear division	6/409	53/18670	1.0e-03	1.9e-02	1.6e-02
GO:0070228	regulation of lymphocyte apoptotic process	6/409	53/18670	1.0e-03	1.9e-02	1.6e-02
GO:1902099	regulation of metaphase/anaphase transition of cell cycle	6/409	53/18670	1.0e-03	1.9e-02	1.6e-02
GO:0032496	response to lipopolysaccharide	17/409	330/18670	1.0e-03	1.9e-02	1.7e-02
GO:0050727	regulation of inflammatory response	22/409	485/18670	1.1e-03	2.1e-02	1.8e-02
GO:0007135	meiosis II	3/409	10/18670	1.1e-03	2.1e-02	1.8e-02
GO:0061983	meiosis II cell cycle process	3/409	10/18670	1.1e-03	2.1e-02	1.8e-02
GO:0007091	metaphase/anaphase transition of mitotic cell cycle	6/409	54/18670	1.1e-03	2.1e-02	1.8e-02
GO:0002714	positive regulation of B cell mediated immunity	5/409	37/18670	1.2e-03	2.2e-02	1.9e-02
GO:0002891	positive regulation of immunoglobulin mediated immune response	5/409	37/18670	1.2e-03	2.2e-02	1.9e-02
GO:0045730	respiratory burst	5/409	37/18670	1.2e-03	2.2e-02	1.9e-02
GO:0051302	regulation of cell division	11/409	168/18670	1.2e-03	2.2e-02	1.9e-02
GO:0051303	establishment of chromosome localization	7/409	75/18670	1.3e-03	2.3e-02	1.9e-02
GO:1990868	response to chemokine	8/409	97/18670	1.3e-03	2.3e-02	2.0e-02
GO:1990869	cellular response to chemokine	8/409	97/18670	1.3e-03	2.3e-02	2.0e-02
GO:0007051	spindle organization	11/409	170/18670	1.3e-03	2.4e-02	2.0e-02
GO:0050000	chromosome localization	7/409	76/18670	1.4e-03	2.4e-02	2.0e-02
GO:0044784	metaphase/anaphase transition of cell cycle	6/409	56/18670	1.4e-03	2.4e-02	2.0e-02
GO:0090307	mitotic spindle assembly	6/409	56/18670	1.4e-03	2.4e-02	2.0e-02
GO:0050764	regulation of phagocytosis	8/409	98/18670	1.4e-03	2.4e-02	2.1e-02
GO:0032753	positive regulation of interleukin-4 production	4/409	23/18670	1.4e-03	2.5e-02	2.1e-02
GO:0036037	CD8-positive, alpha-beta T cell activation	4/409	23/18670	1.4e-03	2.5e-02	2.1e-02
GO:0010965	regulation of mitotic sister chromatid separation	6/409	57/18670	1.5e-03	2.6e-02	2.2e-02
GO:0031652	positive regulation of heat generation	3/409	11/18670	1.5e-03	2.6e-02	2.2e-02
GO:0033089	positive regulation of T cell differentiation in thymus	3/409	11/18670	1.5e-03	2.6e-02	2.2e-02
GO:0045060	negative thymic T cell selection	3/409	11/18670	1.5e-03	2.6e-02	2.2e-02
GO:0033081	regulation of T cell differentiation in thymus	4/409	24/18670	1.7e-03	2.9e-02	2.4e-02
GO:0042104	positive regulation of activated T cell proliferation	4/409	24/18670	1.7e-03	2.9e-02	2.4e-02
GO:0019932	second-messenger-mediated signaling	20/409	439/18670	1.7e-03	2.9e-02	2.5e-02
GO:0002793	positive regulation of peptide secretion	15/409	288/18670	1.8e-03	3.0e-02	2.6e-02
GO:0033045	regulation of sister chromatid segregation	7/409	80/18670	1.8e-03	3.1e-02	2.6e-02
GO:0042267	natural killer cell mediated cytotoxicity	6/409	60/18670	2.0e-03	3.2e-02	2.7e-02
GO:0051306	mitotic sister chromatid separation	6/409	60/18670	2.0e-03	3.2e-02	2.7e-02
GO:0002863	positive regulation of inflammatory response to antigenic stimulus	3/409	12/18670	2.0e-03	3.2e-02	2.7e-02
GO:0043383	negative T cell selection	3/409	12/18670	2.0e-03	3.2e-02	2.7e-02
GO:0046541	saliva secretion	3/409	12/18670	2.0e-03	3.2e-02	2.7e-02
GO:0070601	centromeric sister chromatid cohesion	3/409	12/18670	2.0e-03	3.2e-02	2.7e-02
GO:0050901	leukocyte tethering or rolling	4/409	25/18670	2.0e-03	3.2e-02	2.7e-02
GO:0007218	neuropeptide signaling pathway	8/409	104/18670	2.0e-03	3.3e-02	2.8e-02
GO:2000514	regulation of CD4-positive, alpha-beta T cell activation	6/409	61/18670	2.1e-03	3.4e-02	2.9e-02
GO:2000106	regulation of leukocyte apoptotic process	7/409	83/18670	2.3e-03	3.6e-02	3.1e-02
GO:0002456	T cell mediated immunity	8/409	106/18670	2.3e-03	3.6e-02	3.1e-02
GO:0032623	interleukin-2 production	6/409	62/18670	2.3e-03	3.6e-02	3.1e-02
GO:0045453	bone resorption	6/409	62/18670	2.3e-03	3.6e-02	3.1e-02
GO:1905818	regulation of chromosome separation	6/409	62/18670	2.3e-03	3.6e-02	3.1e-02
GO:0006775	fat-soluble vitamin metabolic process	5/409	43/18670	2.4e-03	3.7e-02	3.2e-02
GO:0050850	positive regulation of calcium-mediated signaling	5/409	43/18670	2.4e-03	3.7e-02	3.2e-02
GO:0007062	sister chromatid cohesion	6/409	63/18670	2.5e-03	3.9e-02	3.3e-02
GO:2000401	regulation of lymphocyte migration	6/409	63/18670	2.5e-03	3.9e-02	3.3e-02
GO:0031650	regulation of heat generation	3/409	13/18670	2.5e-03	3.9e-02	3.3e-02
GO:0045086	positive regulation of interleukin-2 biosynthetic process	3/409	13/18670	2.5e-03	3.9e-02	3.3e-02
GO:0050663	cytokine secretion	13/409	240/18670	2.5e-03	3.9e-02	3.3e-02
GO:0033046	negative regulation of sister chromatid segregation	5/409	44/18670	2.6e-03	4.0e-02	3.4e-02
GO:0042742	defense response to bacterium	16/409	330/18670	2.7e-03	4.0e-02	3.4e-02
GO:0032673	regulation of interleukin-4 production	4/409	27/18670	2.7e-03	4.0e-02	3.4e-02
GO:0002228	natural killer cell mediated immunity	6/409	64/18670	2.7e-03	4.1e-02	3.5e-02
GO:0016445	somatic diversification of immunoglobulins	6/409	64/18670	2.7e-03	4.1e-02	3.5e-02
GO:0046579	positive regulation of Ras protein signal transduction	6/409	64/18670	2.7e-03	4.1e-02	3.5e-02
GO:0051985	negative regulation of chromosome segregation	5/409	45/18670	2.9e-03	4.3e-02	3.7e-02
GO:0050921	positive regulation of chemotaxis	9/409	135/18670	2.9e-03	4.3e-02	3.7e-02
GO:0002548	monocyte chemotaxis	6/409	65/18670	3.0e-03	4.3e-02	3.7e-02
GO:1903046	meiotic cell cycle process	11/409	188/18670	3.0e-03	4.3e-02	3.7e-02
GO:0000075	cell cycle checkpoint	12/409	216/18670	3.0e-03	4.3e-02	3.7e-02
GO:0010818	T cell chemotaxis	4/409	28/18670	3.1e-03	4.4e-02	3.8e-02
GO:0032196	transposition	4/409	28/18670	3.1e-03	4.4e-02	3.8e-02
GO:0032770	positive regulation of monooxygenase activity	4/409	28/18670	3.1e-03	4.4e-02	3.8e-02
GO:0050920	regulation of chemotaxis	12/409	217/18670	3.1e-03	4.4e-02	3.8e-02
GO:0050862	positive regulation of T cell receptor signaling pathway	3/409	14/18670	3.2e-03	4.5e-02	3.9e-02
GO:0070098	chemokine-mediated signaling pathway	7/409	88/18670	3.2e-03	4.5e-02	3.9e-02
GO:0045931	positive regulation of mitotic cell cycle	10/409	163/18670	3.2e-03	4.6e-02	3.9e-02
GO:0050868	negative regulation of T cell activation	8/409	112/18670	3.2e-03	4.6e-02	3.9e-02
GO:0032465	regulation of cytokinesis	7/409	89/18670	3.4e-03	4.8e-02	4.1e-02
GO:0035025	positive regulation of Rho protein signal transduction	4/409	29/18670	3.5e-03	4.9e-02	4.1e-02
GO:0007093	mitotic cell cycle checkpoint	10/409	165/18670	3.5e-03	4.9e-02	4.1e-02
GO:0002204	somatic recombination of immunoglobulin genes involved in immune response	5/409	47/18670	3.5e-03	4.9e-02	4.1e-02
GO:0002208	somatic diversification of immunoglobulins involved in immune response	5/409	47/18670	3.5e-03	4.9e-02	4.1e-02
GO:0030261	chromosome condensation	5/409	47/18670	3.5e-03	4.9e-02	4.1e-02
GO:0045190	isotype switching	5/409	47/18670	3.5e-03	4.9e-02	4.1e-02
GO:0002791	regulation of peptide secretion	21/409	500/18670	3.5e-03	4.9e-02	4.1e-02
GO:0051304	chromosome separation	7/409	90/18670	3.6e-03	4.9e-02	4.2e-02
GO:0071674	mononuclear cell migration	7/409	90/18670	3.6e-03	4.9e-02	4.2e-02

Tabla 12: GOtable que contiene las vías metabólicas expresadas diferencialmente entre los grupos SFI y ELI.

De forma análoga a las toptables, las pathwaytables o GOtables también contienen demasiada información. Una solución mucho más visual consiste en construir un barplot y un cnetplot para cada una de las comparaciones. A continuación se muestran los barplots (Figura 4) y los cnetplots (Figura 5) corresondientes a cada una de las tablas que se acaban de presentar. En el caso de los barplots, las barras están ordenadas de mayor a menor evidencia de que esa vía este diferencialmente expresada.

Figura 4: barplots que muestran las 10 vías metabólicas con mayor evidencia de estar diferencialmente expresadas en las comparaciones NIT-SFI (A), NIT-ELI (B) y SFI-ELI (C).

Figura 5: cnetplots que muestran las 4 vías metabólicas con mayor evidencia de estar diferencialmente expresadas en las comparaciones NIT-SFI (A), NIT-ELI (B) y SFI-ELI (C).

Para comentar y analizar estos resultados obtenidos, lo haremos comparación a comparación. Empezaremos -pues- por la comparación NIT-SFI. Si nos fijamos en los outputs de la GOtable (Tabla 10), el barplot (Figura 4.A) y el cnetplot (Figura 5.A) podemos identificar que las 4 rutas metabólicas que tienen una mayor evidencia de estar parcialmente diferencialmente expresadas están relacionadas con la respuesta inmune. En concreto estas vías están implicadas en la activación, señalización y la proliferación de los limfocitos B y en la respuesta inmune de tipo humoral. Adicionalmente es importante remarcar que la cantidad de genes diferencialmente expresados entre conidiciones oscila alrededor de 10 por vía y que todos estos genes se encuentran infraexpresados para la condición SFI.

Sigamos con la comparación NIT-ELI (Tabla 11, Figura 4.B, Figura 5.B). Analizando los resultados generados, identificamos que las 4 rutas con una mayor evidencia de estar diferencialmente expresadas también están relacionadas con la respuesta inmune. Sin embargo, esta vez las vías están más ligadas a los limfocitos T que a los B. Concretamente, las vías afectadas tienen relación con la activación y diferenciación de los limfocitos T aunque también de otro tipo de limfocitos. Para cada una de estas vías el número de genes diferencialmente expresados oscila entre 58 y 94. Otro hecho que podemos observar y que es muy interesante, es que todos estos genes están infraexpresados en la condición EFI menos tres (TAC1, IHH, IL6).

Finalmente, para la comparación SFI-ELI (Tabla 12, Figura 4.C, Figura 5.C) vemos que 2 de las 4 rutas con una mayor evidencia de estar diferencialmente expresadas son las mismas que vimos para la comparación NIT-ELI. En cuanto a las otras dos, estas tienen una relación muy estrecha con las que se observaron para la comparación anterior. Las vías afectadas están relacionadas con la activación de los limfocitos T y con la activación y regulación de otros limfocitos. El número de genes afectados para cada una de estas vías se mueve dentro del intervalo [48, 61]. Además, si miramos el cnetplot podemos ver que -de nuevo- sólo tres genes están sobrexpresados (IGF1, IL6, TAC1), estando dos de ellos compartidos con la comparación anterior.

Discusión

En cualquier proyecto de investigación, la discusión de los resultados y la extracción de conclusiones requieren de un conocimiento exhaustivo del contexto biológico del estudio. Sin embargo, obtener el grado adecuado de este conocimiento puede implicar meses o años realizando investigación en una misma dirección. Por ese motivo, con mucha frecuencia, el papel del bioinformático pasa a un segundo plano en esta parte del proceso de investigación. Su papel, pues, consiste básicamente en ofrecer soporte al resto del equipo, generar un informe con los resultados y, dentro de lo posible, comentarlos. Aunque en la sección de resultados ya hemos realizado una breve discusión de estos, hemos decidido presentar -a continuación- una valoración general.

A diferencia de la PEC 1, donde nos intentamos basar en los métodos propuestos por el personal docente, en este caso hemos intendado improvisar un poco y utilizar aquellas pruebas/análisis y aquellos paquetes/librerías que más nos han convenido. Aunque no es mi intención utilizar esto como excusa, debido a temas laborales que han implicado emigrar a otro país, para algunos de los análisis hemos utilizado paquetes que -a priori- pueden parecer relativamente antiguos. La velocidad con la que avanzan las diferentes ramas de la bioinformática y la aparición constante de nuevos paquetes sumada a la falta de tiempo ha hecho que hayamos intendado simplificar el workflow de análisis.

A pesar de todo lo comentado anteriormente, hemos obtenido unos resultados que podemos considerar -como mínimo- interesantes. A continuación pasamos a comentarlos. Según los datos obtenidos, la expresión diferencial entre las condiciones NIT (control) y SFI (infilitraciones focales) es poco significativa. La aplicación de infilitraciones focales en el tejido tiroide afecta solo a un 0.71% de los genes, estando un 0.11% de ellos sobrexpresados y un 0.6% infraexpresados (Tabla 7, Figura 3.A). En contraste, si nos fijamos en las dos otras comparaciones, observamos que la aplicación de infiltraciones extensivas provoca una expresión diferencial significativa. Respecto al control, esta aplicación afecta la expresión de un 8.1% de los genes, estando un 2% sobrexpresados y un 6.1% infraexpresados. En cambio, respecto al grupo con infiltraciones focales, vemos que esta aplicación afecta la expresión del 8.9% de los genes. En síntonia con lo observado para la comparación NIT vs SFI, la mayoría de estos genes están infraexpresados (6.1% frente a 2.8%). Los volcano plots secundan estas conclusiones y nos permiten asimilar estas ideas de forma más visual.

Aunque los resultados que acabamos de presentar son muy interesantes y válidos, para sacar conclusiones es más conveniente traducir estos resultados de genes a vías metabólicas diferencialmente expresadas. La generación de pathwaytables y -a partir de estas- de barplots y cnetplots revela que en cualquiera de las tres comparaciones las vías metabólicas afectadas tienen relación con la respuesta inmune. Más concretamente con la activación, proliferación y diferenciación de los limfocitos B y T. Es importante destacar que para la comparación NIT-SFI, la mayoría de genes afectados están más relacionados con los limfocitos B mientras que para las otras dos comparaciones lo están para los T. Adicionalmente, como ya hemos visto anteriormente, casi todos los genes están infraexpresados. Sin embargo, para las comparaciones NIT-ELI y SFI-ELI, tres genes están sobrexpresados. Estos son IL6 y TAC1 (compartidos) y IGF1 (SFI-ELI) o RUNX3 (NIT-ELI). En consecuencia, podría ser interesante ver que función tienen estos genes y porque están sobrexpresados.

En síntesi, la aplicación de infiltraciones focales en el tejido tiroideo tienen un efecto significativamente leve sobre la respuesta inmune, provocando la infraexpresión de un número pequeño de genes. Sin embargo, la aplicación de inflitraciones extensivas tiene un efecto mucho más potente, provocando la infraexpresión de un número mucho más considerable de genes relacionados también con la respuesta inmune. Finalmente, si comparamos el grupo con extensiones focales y extensivas obtenemos unos resultados muy parecidos a los obtenidos entre el control y el segundo grupo.

Annexo

A continuación se muestra todo el código que hemos utilizado para este análisis. Este contenido es idéntico a aquel presente dentro del script Garcia_Marc_ADO_PEC2.R.

# PEC2: Análisis de Datos Ómicos

# ------------------------------------------------------------------------------------------------------------------------------------------------------

# Estableciendo el directorio de trabajo

setwd("C:/Users/USER/Documents/Màster Bioestadística i Bioinfo/Análisis de datos Ómicos/PECS/ADO_PEC2_Marc_Garcia/")

# -------------------------------------------------------------------------------------------------------------------------------------------------------

# Preparando el entorno de trabajo 

dir.create("data")
dir.create("scripts")
dir.create("results")
dir.create("other")
dir.create("figures")

# -------------------------------------------------------------------------------------------------------------------------------------------------------

# Carga de paquetes

# 1) CRAN

library(readxl)
library(ggplot2)
library(ggrepel)
library(viridis)
library(magrittr)
library(cowplot)
library(cluster)
library(factoextra)

# 2) Bioconductor

library(Biobase)
library(DESeq2)
library(AnnotationDbi)
library(EnhancedVolcano)
library(org.Hs.eg.db)
library(clusterProfiler)
library(ReactomePA)
library(enrichplot)

# -----------------------------------------------------------------------------------------------------------------------------------------------------

# Cargando los datos

counts_raw <- read.csv(file = "data/counts.csv", 
                       sep = ";", 
                       header = T, 
                       row.names = 1, 
                       stringsAsFactors = F, 
                       check.names = F) 

targets_file <- read.csv(file = "data/targets.csv", 
                         sep = ",")

# -----------------------------------------------------------------------------------------------------------------------------------------------------

# Exploración raw counts + targets file

# 1) Raw counts

dim(counts_raw)                                                                       
View(counts_raw)                                                                      
head(counts_raw[ , 1:4], 8)                                                           

# 2) Targets

dim(targets_file)                                                                     
View(targets_file)                                                                    
head(targets_file, 10)                                                                

# ----------------------------------------------------------------------------------------------------------------------------------------------------

# Preprocesado de los datos

# 1) Selección de las muestras

targets_file_nit <- targets_file[targets_file$Group == "NIT", ]                       
targets_file_sfi <- targets_file[targets_file$Group == "SFI", ]                       
targets_file_eli <- targets_file[targets_file$Group == "ELI", ]                       

sample_names_nit <- as.character(targets_file_nit$Sample_Name)                        
sample_names_sfi <- as.character(targets_file_sfi$Sample_Name)                        
sample_names_eli <- as.character(targets_file_eli$Sample_Name)                        

set.seed(65261)                                                                         
nit_subset <- sample(x = sample_names_nit, size = 10, replace = F)                     
sfi_subset <- sample(x = sample_names_sfi, size = 10, replace = F)                    
eli_subset <- sample(x = sample_names_eli, size = 10, replace = F)                    
selected_samples <- c(nit_subset, sfi_subset, eli_subset)                             

# 2) Subsetting

# 2.1) Counts

counts_raw_sub <- counts_raw[ , selected_samples]                                     

# 2.2) Targets

rownames(targets_file) <- targets_file$Sample_Name                                    
targets_raw_sub <- targets_file[selected_samples, ]

# 3) Cambio de nombre de las muestras

colnames(counts_raw_sub)[1:10] <- paste0("NIT_", 1:10)                                
colnames(counts_raw_sub)[11:20] <- paste0("SFI_", 1:10)                               
colnames(counts_raw_sub)[21:30] <- paste0("ELI_", 1:10)                               
rownames(targets_raw_sub) <- colnames(counts_raw_sub)
targets_raw_sub$color <- c(rep("#238A8DFF", 10), rep("#DCE319FF", 10), rep("#481567FF", 10))

# 4) Comprobaciones

head(counts_raw_sub[1:17], 10)
colnames(counts_raw_sub)
rownames(targets_raw_sub)

# 5) Guardando los subsets

# 5.1) Counts

write.csv(x = counts_raw_sub, 
          file = "data/counts_sub.csv", 
          row.names = T)

# 5.2) Targets

write.csv(x = targets_raw_sub, 
          file = "data/targets_sub.csv", 
          row.names = T)
  
# ----------------------------------------------------------------------------------------------------------------------------------------------------

# Construcción de un objeto DESeq dataset

count_data <- read.csv("data/counts_sub.csv", row.names = 1)
col_data <- read.csv("data/targets_sub.csv", row.names = 1)

(dds_mat <- DESeqDataSetFromMatrix(countData = count_data, 
                                   colData = col_data, 
                                   design = ~ Group))

# --------------------------------------------------------------------------------------------------------------------------

# Eliminando genes no expresados

(dds_mat_filtered <- dds_mat[rowSums(counts(dds_mat)) >= 1, ])
filtered_out <- nrow(dds_mat) - nrow(dds_mat_filtered)

# --------------------------------------------------------------------------------------------------------------------------

# Transformación vst

vsd <- vst(object = dds_mat_filtered, blind = FALSE)
head(assay(vsd), 10)[ , 1:10]

# --------------------------------------------------------------------------------------------------------------------------

# Control de calidad

# 1) Boxplot

dir.create("figures/boxplots")

(g1 <- ggplot(stack(data.frame(assay(vsd))), aes(x = ind, y = values, fill = ind)) +
  geom_boxplot() +
  scale_fill_manual(values = targets_raw_sub$color) +
    labs(title = "Boxplot transformed counts", 
         x = "muestra", 
         y = "pseudocounts") +
    theme_classic() +
    theme(legend.position = "none", axis.text.x = element_text(angle = 90, hjust = 1)) +
    theme(axis.title.y = element_text(margin = margin(t = 0, r = 10, b = 0, l = 0)),
          axis.title.x = element_text(margin = margin(t = 10, r = 0, b = 0, l = 0))))

tiff("figures/boxplots/pseudocount_raw.tiff", 
     res = 300, 
     width = 5.5, 
     height = 5.5, 
     units = 'in', 
     bg = NA)

print(g1)

dev.off()

# 2) PCA plot

plotPCA3 <- function (datos, labels, factor, title, scale, size = 1.5, glineas = 0.25) {
  
  data <- prcomp(t(datos), scale = scale)
  
  # plot adjustments
  
  dataDf <- data.frame(data$x)
  Group <- factor
  loads <- round(data$sdev^2/sum(data$sdev^2) * 100, 1)
  
  # main plot
  
  p1 <- ggplot(data = dataDf, aes(x = PC1, y = PC2)) +
    theme_classic() +
    geom_hline(yintercept = 0, color = "gray70") +
    geom_vline(xintercept = 0, color = "gray70") +
    geom_point(aes(color = Group), size = 2) +
    coord_cartesian(xlim = c(min(data$x[ , 1]) - 5, max(data$x[ , 1]) + 5)) +
    scale_fill_discrete(name = "Group") +
    theme(axis.title.y = element_text(size = 10,
                                      margin = margin(t = 0, r = 10, b = 0, l = 0)),
          axis.title.x = element_text(size = 10,
                                      margin = margin(t = 10, r = 0, b = 0, l = 0)),
          axis.text = element_text(size = 7), 
          legend.text = element_text(size = 8),
          legend.title = element_text(size = 10),
          legend.key.size = unit(0.4, "cm"),
          legend.key.width = unit(0.5,"cm")) 
  
  # avoiding labels superposition
  
  p1 + geom_text_repel(aes(y = PC2 + 0.25, label = labels), segment.size = 0.25, size = size) + 
    labs(x = c(paste("PC1", loads[1], "%")), y = c(paste("PC2", loads[2], "%"))) +  
    ggtitle(paste("PCA for: ", title, sep = " ")) + 
    scale_color_viridis(discrete = T)
}

dir.create("figures/PCA_plots")

tiff("figures/PCA_plots/PCA_raw.tiff", 
       res = 300, 
       width = 5.5, 
       height = 5.5, 
       units = 'in', 
       bg = NA)
  
print(plotPCA3(datos = assay(vsd), 
                 labels = colnames(counts_raw_sub), 
                 factor = targets_raw_sub$Group, 
                 title = "transformed counts", 
                 scale = F, 
                 size = 2.5))

dev.off()

# 3) Dendrograma

sample_dist <- dist(t(assay(vsd)))
res <- hcut(sample_dist, k = 2, stand = T, method = "euclidean")
res$labels <- as.character(colnames(dds_mat_filtered))

dir.create("figures/dendrograms")

tiff("figures/dendrograms/dendrogram.tiff", 
     res = 300, 
     width = 10, 
     height = 5.5, 
     units = 'in', 
     bg = NA)

print(fviz_dend(res, 
                rect = T, 
                cex = 0.5, 
                lwd = 1, 
                k_colors = c("#440154FF", "#FDE725FF"), 
                label_cols = "black"))

dev.off()

# -------------------------------------------------------------------------------------------------------------------------

# Selección de genes diferencialmente expresados (DEG) 

# 1) Construyendo DESeq2DataSet

dds_mat <- DESeqDataSetFromMatrix(countData = count_data, 
                                  colData = col_data, 
                                  design = ~ Group)

# 2) Filtrando genes que cierta expresión

dds_mat_filtered <- dds_mat[rowSums(counts(dds_mat)) >= 1, ]

# 3) Creación de objeto DESeq

dds <- DESeq(dds_mat_filtered, parallel = T)

# 4) Contrastes

# 4.1) NIT vs SFI

# 4.1.1) Generando resultados contraste

res_1 <- results(dds, contrast = c("Group","NIT","SFI"))

# 4.1.2) Modificando los ENSEMBL gene ids

rownames(res_1) <- gsub("\\..*","", rownames(res_1))

# 4.1.3) Consultando resumen de los resultados (padj < 0.1)

summary_1 <- summary(res_1, alpha = 0.1)

# 4.1.4) Anotando DEG (genesymbol + entrezid)

res_1$symbol <- mapIds(x = org.Hs.eg.db, 
                       keys = rownames(res_1), 
                       column = "SYMBOL", 
                       keytype = "ENSEMBL", 
                       multiVals = "first")

res_1$entrez <- mapIds(x = org.Hs.eg.db,
                       keys = rownames(res_1),
                       column = "ENTREZID",
                       keytype = "ENSEMBL",
                       multiVals="first")

# 4.1.5) Eliminando genes que no tienen anotación

res_1 <- na.omit(res_1)

# 4.1.6) Guardando el contenido de la toptable

dir.create("results/top_taples")

write.csv(x = res_1, 
          file = "results/top_taples/top_table_NITvsSFI.csv", 
          row.names = T)

# 4.1.7) Filtrando DEG (log2FC > 2 & padj < 0.1)

res_1_filtered <- as.data.frame(res_1)[which(res_1$padj < 0.1 & abs(res_1$log2FoldChange) > 2), ]
res_1_filtered <- res_1_filtered[order(res_1_filtered$padj), ]
View(res_1_filtered)

# 4.1.8) Guardando el contenido de la toptable filtrada

dir.create("results/top_tables_filtered")

write.csv(x = res_1_filtered, 
          file = "results/top_tables_filtered/top_table_NITvsSFI_filtered.csv", 
          row.names = T)

# 4.1.9) Volcano plot

dir.create("figures/volcano_plots")

tiff(filename = "figures/volcano_plots/volcano_plot_NITvsSFI.tiff", 
     width = 5.5, 
     height = 5.5, 
     res = 300, 
     units = "in")

print(EnhancedVolcano(toptable = res_1, 
                      lab = res_1$symbol,
                      selectLab = res_1$symbol[order(res_1$padj)][1:5],
                      x = "log2FoldChange", 
                      y = "padj", 
                      pCutoff = 0.1, 
                      FCcutoff = 1,
                      ylim = c(0, 7), 
                      xlim = c(-7, 5), 
                      pointSize = 1.7,
                      axisLabSize = 13,
                      labSize = 4,
                      subtitle = "",
                      caption = "",
                      title = "NIT vs SFI", 
                      titleLabSize = 18, 
                      legendVisible = F,
                      legendPosition = "bottom", 
                      legendLabSize = 10, 
                      legendIconSize = 3))

dev.off()

# 4.1.10) heatmap

dir.create("figures/heatmaps")

h_res_1 <- as.matrix(counts_raw_sub[rownames(res_1_filtered), 1:20])
rownames(h_res_1) <- res_1_filtered$symbol

tiff(filename = "figures/heatmaps/heatmap_NITvsSFI.tiff", 
     width = 5.5, 
     height = 5.5, 
     res = 300, 
     units = "in")

heatmap(h_res_1)

dev.off()

# 4.2) NIT vs ELI

# 4.2.1) Generando resultados contraste

res_2 <- results(dds, contrast = c("Group", "NIT", "ELI"))

# 4.2.2) Modificando los ENSEMBL gene ids

rownames(res_2) <- gsub("\\..*","", rownames(res_2))

# 4.2.3) Consultando resumen de los resultados (padj < 0.1)

summary_1 <- summary(res_2, alpha = 0.1)

# 4.2.4) Anotando DEG

res_2$symbol <- mapIds(x = org.Hs.eg.db, 
                       keys = rownames(res_2), 
                       column = "SYMBOL", 
                       keytype = "ENSEMBL", 
                       multiVals = "first")

res_2$entrez <- mapIds(x = org.Hs.eg.db,
                       keys = rownames(res_2),
                       column = "ENTREZID",
                       keytype = "ENSEMBL",
                       multiVals="first")

# 4.2.5) Eliminando genes que no tienen anotación

res_2 <- na.omit(res_2)

# 4.2.6) Guardando el contenido de la toptable

write.csv(x = res_2, 
          file = "results/top_taples/top_table_NITvsELI.csv", 
          row.names = T)

# 4.2.7) Filtrando DEG (log2FC > 2 & padj < 0.1)

res_2_filtered <- as.data.frame(res_2)[which(res_2$padj < 0.1 & abs(res_2$log2FoldChange) > 2), ]
res_2_filtered <- res_2_filtered[order(res_2_filtered$padj), ]
View(res_2_filtered)

# 4.2.8) Guardando contenido de la toptable filtrada

write.csv(x = res_2_filtered, 
          file = "results/top_tables_filtered/top_table_NITvsELI_filtered.csv", 
          row.names = T)

# 4.2.9) Volcano plot

tiff(filename = "figures/volcano_plots/volcano_plot_NITvsELI.tiff", 
     width = 5.5, 
     height = 5.5, 
     res = 300, 
     units = "in")

print(EnhancedVolcano(toptable = res_2, 
                      lab = res_2$symbol,
                      selectLab = res_2$symbol[order(res_2$padj)][1:5],
                      x = "log2FoldChange", 
                      y = "padj", 
                      pCutoff = 0.1, 
                      FCcutoff = 1,
                      ylim = c(0, 30), 
                      xlim = c(-10, 5), 
                      pointSize = 1.7,
                      axisLabSize = 13,
                      labSize = 4,
                      subtitle = "",
                      caption = "",
                      title = "NIT vs ELI", 
                      titleLabSize = 18, 
                      legendVisible = F,
                      legendPosition = "bottom", 
                      legendLabSize = 10, 
                      legendIconSize = 3))

dev.off()

# 4.2.10) heatmap

h_res_2 <- as.matrix(counts_raw_sub[rownames(res_2_filtered), 1:20])
rownames(h_res_2) <- res_2_filtered$symbol

tiff(filename = "figures/heatmaps/heatmap_NITvsSFI.tiff", 
     width = 5.5, 
     height = 5.5, 
     res = 300, 
     units = "in")

heatmap(h_res_2)

dev.off()

# 4.3) SFI vs ELI

# 4.3.1) Generando resultados contraste

res_3 <- results(dds, contrast = c("Group", "SFI", "ELI"))

# 4.3.2) Modificando los ENSEMBL gene ids

rownames(res_3) <- gsub("\\..*","", rownames(res_3))

# 4.3.3) Consultando resumen de los resultados (padj < 0.1)

summary_3 <- summary(res_3, alpha = 0.1)

# 4.3.4) Anotando DEG

res_3$symbol <- mapIds(x = org.Hs.eg.db, 
                       keys = rownames(res_3), 
                       column = "SYMBOL", 
                       keytype = "ENSEMBL", 
                       multiVals = "first")

res_3$entrez <- mapIds(x = org.Hs.eg.db,
                       keys = rownames(res_3),
                       column = "ENTREZID",
                       keytype = "ENSEMBL",
                       multiVals="first")

# 4.3.5) Eliminando genes que no tienen anotación

res_3 <- na.omit(res_3)

# 4.3.6) Guardando el contenido de la toptable

write.csv(x = res_3, 
          file = "results/top_taples/top_table_SFIvsELI.csv", 
          row.names = T)

# 4.3.7) Filtrando DEG (log2FC > 2 & padj < 0.1)

res_3_filtered <- as.data.frame(res_3)[which(res_3$padj < 0.1 & abs(res_3$log2FoldChange) > 2), ]
res_3_filtered <- res_3_filtered[order(res_3_filtered$padj), ]
View(res_filtered)

# 4.3.8) Guardando contenido de la toptable filtrada

write.csv(x = res_3_filtered, 
          file = "results/top_tables_filtered/top_table_SFIvsELI_filtered.csv", 
          row.names = T)

# 4.3.9) Volcano plot

tiff(filename = "figures/volcano_plots/volcano_plot_SFIvsELI.tiff", 
     width = 5.5, 
     height = 5.5, 
     res = 300, 
     units = "in")

print(EnhancedVolcano(toptable = res_3, 
                      lab = res_3$symbol,
                      selectLab = res_3$symbol[order(res_3$padj)][1:5],
                      x = "log2FoldChange", 
                      y = "padj", 
                      pCutoff = 0.1, 
                      FCcutoff = 1,
                      ylim = c(0, 15), 
                      xlim = c(-10, 5), 
                      pointSize = 1.7,
                      axisLabSize = 13,
                      labSize = 4,
                      subtitle = "",
                      caption = "",
                      title = "SFI vs ELI", 
                      titleLabSize = 18, 
                      legendVisible = F,
                      legendPosition = "bottom", 
                      legendLabSize = 10, 
                      legendIconSize = 3))

dev.off()

# 4.3.10) heatmap

h_res_3 <- as.matrix(counts_raw_sub[rownames(res_3_filtered), 1:20])
rownames(h_res_3) <- res_3_filtered$symbol

tiff(filename = "figures/heatmaps/heatmap_NITvsSFI.tiff", 
     width = 5.5, 
     height = 5.5, 
     res = 300, 
     units = "in")

heatmap(h_res_3)

legend("topright",     
       legend = c("NIT", "SFI"), 
       col = c("royalblue3","goldenrod"),
       lty = 1,
       lwd = 10)

dev.off()

# -------------------------------------------------------------------------------------------------------------------------

# Análisis de significación (gene enrichment analysis)

# 1) NIT vs SFI

dir.create("results/GO_tables")
dir.create("figures/cnet_plots")
dir.create("figures/bar_plots")

entrez_res_1 <- res_1_filtered$entrez

res_1_enriched <- enrichGO(gene = entrez_res_1,
                           OrgDb = org.Hs.eg.db,
                           ont = "BP",
                           pAdjustMethod = "BH",
                           pvalueCutoff = 0.05, 
                           qvalueCutoff = 0.05,
                           readable = TRUE)

GO_table_res_1 <- as.data.frame(res_1_enriched@result)[ , 1:7]
GO_table_res_1 <- GO_table_res_1[GO_table_res_1$p.adjust < 0.05 & GO_table_res_1$qvalue < 0.05, ]
View(GO_table_res_1)

write.csv(x = GO_table_res_1, 
          file = "results/GO_tables/GO_table_NITvsSFI.csv", 
          row.names = T)

tiff(filename = "figures/bar_plots/bar_plot_NITvsSFI.tiff", 
     width = 15, 
     height = 8, 
     res = 300, 
     units = "in")

barplot(res_1_enriched, showCategory = 10) 

dev.off()

logFC <- res_1_filtered$log2FoldChange[res_1_filtered$padj < 0.05]
names <- res_1_filtered$symbol[res_1_filtered$padj < 0.05]
vec <- setNames(logFC, names)

tiff(filename = "figures/cnet_plots/cnet_plot_NITvsSFI.tiff", 
     width = 7.5, 
     height = 7, 
     res = 300, 
     units = "in")

cnetplot(x = res_1_enriched, 
         node_label = "all", 
         showCategory = 5, 
         foldChange = vec, 
         layout = "kk", 
         circular = F)

dev.off()

# 2) NIT vs ELI

entrez_res_2 <- res_2_filtered$entrez

res_2_enriched <- enrichGO(gene = entrez_res_2,
                           OrgDb = org.Hs.eg.db,
                           ont = "BP",
                           pAdjustMethod = "BH",
                           pvalueCutoff = 0.05, 
                           qvalueCutoff = 0.05,
                           readable = TRUE)

GO_table_res_2 <- as.data.frame(res_2_enriched@result)[ , 1:7]
GO_table_res_2 <- GO_table_res_2[GO_table_res_2$p.adjust < 0.05 & GO_table_res_2$qvalue < 0.05, ]
View(GO_table_res_2)

write.csv(x = GO_table_res_2, 
          file = "results/GO_tables/GO_table_NITvsELI.csv", 
          row.names = T)

tiff(filename = "figures/bar_plots/bar_plot_NITvsELI.tiff", 
     width = 15, 
     height = 8, 
     res = 300, 
     units = "in")

barplot(res_2_enriched, showCategory = 10) 

dev.off()

logFC <- res_2_filtered$log2FoldChange[res_2_filtered$padj < 0.05]
names <- res_2_filtered$symbol[res_2_filtered$padj < 0.05]
vec <- setNames(logFC, names)

tiff(filename = "figures/cnet_plots/cnet_plot_NITvsELI.tiff", 
     width = 7.5, 
     height = 7, 
     res = 300, 
     units = "in")

cnetplot(x = res_2_enriched, 
         node_label = "all", 
         showCategory = 4, 
         foldChange = vec, 
         layout = "kk", 
         circular = F)

dev.off()

# 3) SFI vs ELI

entrez_res_3 <- res_3_filtered$entrez

res_3_enriched <- enrichGO(gene = entrez_res_3,
                           OrgDb = org.Hs.eg.db,
                           ont = "BP",
                           pAdjustMethod = "BH",
                           pvalueCutoff = 0.15,
                           readable = TRUE)

GO_table_res_3 <- as.data.frame(res_3_enriched@result)[ , 1:7]
GO_table_res_3 <- GO_table_res_3[GO_table_res_3$p.adjust < 0.05 & GO_table_res_3$qvalue < 0.05, ]
View(GO_table_res_3)

write.csv(x = GO_table_res_3, 
          file = "results/GO_tables/GO_table_SFIvsELI.csv", 
          row.names = T)

tiff(filename = "figures/bar_plots/bar_plot_SFIvsELI.tiff", 
     width = 15, 
     height = 8, 
     res = 300, 
     units = "in")

barplot(res_3_enriched, showCategory = 10) 

dev.off()

logFC <- res_3_filtered$log2FoldChange[res_3_filtered$padj < 0.05]
names <- res_3_filtered$symbol[res_3_filtered$padj < 0.05]
vec <- setNames(logFC, names)

tiff(filename = "figures/cnet_plots/cnet_plot_SFIvsELI.tiff", 
     width = 7.5, 
     height = 7, 
     res = 300, 
     units = "in")

cnetplot(x = res_3_enriched, 
         node_label = "all", 
         showCategory = 4, 
         foldChange = vec, 
         layout = "kk", 
         circular = F)

dev.off()

Referencias

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Yu, Guangchuang. 2019. Enrichplot: Visualization of Functional Enrichment Result. https://github.com/GuangchuangYu/enrichplot.